|
|
call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__000114385901302__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__000114385901302__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:30772","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__000114385901302__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"000114385901302","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__000114385901302__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol Marvin 09290509533D starting HoverWatcher_5 Time for openFile( Marvin 09290509533D 14 13 0 0 0 0 999 V2000 1.3187 -3.1154 1.6151 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0129 -1.8759 1.0478 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0685 -2.3057 0.0274 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7480 -1.0823 -0.5386 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7313 -1.2201 -1.4679 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4049 0.0209 -0.1790 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8634 -3.4633 2.5189 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3177 -3.9214 0.8502 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2723 -2.8608 1.8885 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5020 -1.3152 1.8728 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2615 -1.2252 0.5515 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5844 -2.8697 -0.7984 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8274 -2.9496 0.5212 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1764 -0.3997 -1.8590 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 4 6 2 0 0 0 0 7 1 1 0 0 0 0 8 1 1 0 0 0 0 9 1 1 0 0 0 0 10 2 1 0 0 0 0 11 2 1 0 0 0 0 12 3 1 0 0 0 0 13 3 1 0 0 0 0 14 5 1 0 0 0 0 M END): 16 ms reading 14 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 14 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
|
| Butyric acid (; from Ancient Greek: βούτῡρον, meaning "butter"), also known under the systematic name butanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula CH3CH2CH2COOH. It is an oily, colorless liquid with an unpleasant odor. Isobutyric acid (2-methylpropanoic acid) is an isomer. Salts and esters of butyric acid are known as butyrates or butanoates. The acid does not occur widely in nature, but its esters are widespread. It is a common industrial chemical and an important component in the mammalian gut.
|
|
Read full article at Wikipedia
|
| InChI=1S/C4H8O2/c1-2-3-4(5)6/h2-3H2,1H3,(H,5,6) |
| FERIUCNNQQJTOY-UHFFFAOYSA-N |
|
|
Mycoplasma genitalium
(NCBI:txid2097)
|
See:
PubMed
|
|
Homo sapiens
(NCBI:txid9606)
|
Found in
saliva
(UBERON:0001836).
See:
PubMed
|
|
Homo sapiens
(NCBI:txid9606)
|
Found in
blood
(UBERON:0000178).
See:
Geigy Scientific Tables, 8th Rev edition, pp. 165-177. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp., Basel, Switzerland c1981-1992.
|
|
Homo sapiens
(NCBI:txid9606)
|
Found in
faeces
(UBERON:0001988).
See:
PubMed
|
|
Homo sapiens
(NCBI:txid9606)
|
Found in
breast milk
(ENVO:02000031).
See:
PubMed
|
|
Homo sapiens
(NCBI:txid9606)
|
Found in
urine
(BTO:0001419).
See:
PubMed
|
|
Homo sapiens
(NCBI:txid9606)
|
Found in
cerebrospinal fluid
(UBERON:0001359).
See:
Geigy Scientific Tables, 8th Rev edition, pp. 165-177. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp., Basel, Switzerland c1981-1992.
|
|
Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
|
|
|
Mycoplasma genitalium metabolite
Any bacterial metabolite produced during a metabolic reaction in Mycoplasma genitalium.
human urinary metabolite
Any metabolite (endogenous or exogenous) found in human urine samples.
|
|
View more via ChEBI Ontology
|
Outgoing
|
butyric acid
(CHEBI:30772)
has role
Mycoplasma genitalium metabolite
(CHEBI:131604)
butyric acid
(CHEBI:30772)
has role
human urinary metabolite
(CHEBI:84087)
butyric acid
(CHEBI:30772)
is a
fatty acid 4:0
(CHEBI:140601)
butyric acid
(CHEBI:30772)
is a
straight-chain saturated fatty acid
(CHEBI:39418)
butyric acid
(CHEBI:30772)
is conjugate acid of
butyrate
(CHEBI:17968)
|
|
|
Incoming
|
α-amino-γ-cyanobutanoic acid
(CHEBI:27578)
has functional parent
butyric acid
(CHEBI:30772)
α-aminobutyric acid
(CHEBI:35621)
has functional parent
butyric acid
(CHEBI:30772)
γ-amino-β-hydroxybutyric acid
(CHEBI:16080)
has functional parent
butyric acid
(CHEBI:30772)
γ-amino-γ-cyanobutanoic acid
(CHEBI:28474)
has functional parent
butyric acid
(CHEBI:30772)
γ-aminobutyric acid
(CHEBI:16865)
has functional parent
butyric acid
(CHEBI:30772)
(2S)-2-[({4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]phenyl}carbonyl)amino]-4-(2H-tetrazol-5-yl)butanoic acid
(CHEBI:43831)
has functional parent
butyric acid
(CHEBI:30772)
(2S)-3-methyl-2-((2R,3S)-3-[(methylsulfonyl)amino]-1-{[2-(pyrrolidin-1-ylmethyl)-1,3-oxazol-4-yl]carbonyl}pyrrolidin-2-yl)butanoic acid
(CHEBI:39551)
has functional parent
butyric acid
(CHEBI:30772)
(2S,3R)-2-[(3S,6R)-3-amino-6-hydroxy-2-oxopiperidinyl]-3-hydroxybutanoic acid
(CHEBI:45661)
has functional parent
butyric acid
(CHEBI:30772)
(R)-2-hydroxy-4-(hydroxymethylphosphinyl)butyric acid
(CHEBI:55544)
has functional parent
butyric acid
(CHEBI:30772)
(R)-3,4-dihydroxy-2-oxobutanoic acid
(CHEBI:137486)
has functional parent
butyric acid
(CHEBI:30772)
(R)-3-[(R)-3-hydroxybutanoyloxy]butanoic acid
(CHEBI:17663)
has functional parent
butyric acid
(CHEBI:30772)
(R)-3-hydroxy-2-oxo-4-phosphonooxybutanoic acid
(CHEBI:27951)
has functional parent
butyric acid
(CHEBI:30772)
(S)-2,4-dihydroxy-3-oxobutanoic acid
(CHEBI:137502)
has functional parent
butyric acid
(CHEBI:30772)
(S)-2-acetyl-2-hydroxybutanoic acid
(CHEBI:27681)
has functional parent
butyric acid
(CHEBI:30772)
(S)-3,4-dihydroxy-2-oxobutanoic acid
(CHEBI:137456)
has functional parent
butyric acid
(CHEBI:30772)
1,2-dibutyryl-sn-glycero-3-phospho-(1ʼD-myo-inositol)
(CHEBI:83240)
has functional parent
butyric acid
(CHEBI:30772)
1,2-dibutyryl-sn-glycero-3-phospho-(1ʼD-myo-inositol-5ʼ-phosphate)
(CHEBI:83239)
has functional parent
butyric acid
(CHEBI:30772)
1-butyryl-2-oleoyl-sn-glycerol
(CHEBI:75443)
has functional parent
butyric acid
(CHEBI:30772)
1-palmitoyl-2-butanoyl-sn-glycero-3-phosphocholine
(CHEBI:77832)
has functional parent
butyric acid
(CHEBI:30772)
2,2,4-trihydroxybutanoic acid
(CHEBI:73967)
has functional parent
butyric acid
(CHEBI:30772)
2,3-dihydroxy-3-methylbutanoic acid
(CHEBI:15689)
has functional parent
butyric acid
(CHEBI:30772)
2,4-diaminobutyric acid
(CHEBI:64307)
has functional parent
butyric acid
(CHEBI:30772)
2-(hydroxymethyl)-4-oxobutanoic acid
(CHEBI:17413)
has functional parent
butyric acid
(CHEBI:30772)
2-acetyllactic acid
(CHEBI:16444)
has functional parent
butyric acid
(CHEBI:30772)
2-amino-2-hydroxybutanoic acid
(CHEBI:74821)
has functional parent
butyric acid
(CHEBI:30772)
2-amino-2-methylbutanoic acid
(CHEBI:28075)
has functional parent
butyric acid
(CHEBI:30772)
2-amino-3-oxobutanoic acid
(CHEBI:17844)
has functional parent
butyric acid
(CHEBI:30772)
2-hydroxybutyric acid
(CHEBI:1148)
has functional parent
butyric acid
(CHEBI:30772)
2-methylacetoacetic acid
(CHEBI:37079)
has functional parent
butyric acid
(CHEBI:30772)
2-oxobutanoic acid
(CHEBI:30831)
has functional parent
butyric acid
(CHEBI:30772)
2-phenylbutyric acid
(CHEBI:86545)
has functional parent
butyric acid
(CHEBI:30772)
3,4-dihydroxybutyric acid
(CHEBI:86371)
has functional parent
butyric acid
(CHEBI:30772)
3-(indol-3-yl)-2-oxobutyric acid
(CHEBI:28549)
has functional parent
butyric acid
(CHEBI:30772)
3-aminobutanoic acid
(CHEBI:37081)
has functional parent
butyric acid
(CHEBI:30772)
3-hydroxy-2-methylbutanoic acid
(CHEBI:37051)
has functional parent
butyric acid
(CHEBI:30772)
3-hydroxybutyric acid
(CHEBI:20067)
has functional parent
butyric acid
(CHEBI:30772)
3-hydroxyisovaleric acid
(CHEBI:37084)
has functional parent
butyric acid
(CHEBI:30772)
3-methyl-2-oxobutanoic acid
(CHEBI:16530)
has functional parent
butyric acid
(CHEBI:30772)
4-(2-amino-5-hydroxyphenyl)-2,4-dioxobutanoic acid
(CHEBI:28350)
has functional parent
butyric acid
(CHEBI:30772)
4-(2-aminophenyl)-2,4-dioxobutanoic acid
(CHEBI:17442)
has functional parent
butyric acid
(CHEBI:30772)
4-(2-thienyl)butyric acid
(CHEBI:40114)
has functional parent
butyric acid
(CHEBI:30772)
4-(5-ethyl-2-thienyl)-4-oxobutyric acid
(CHEBI:64441)
has functional parent
butyric acid
(CHEBI:30772)
4-(hydroxymethylphosphinyl)-2-oxobutyric acid
(CHEBI:55526)
has functional parent
butyric acid
(CHEBI:30772)
4-(methylamino)butyric acid
(CHEBI:37755)
has functional parent
butyric acid
(CHEBI:30772)
4-[3-(3-nitrophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid
(CHEBI:41198)
has functional parent
butyric acid
(CHEBI:30772)
4-[4-(2,5-dioxopyrrolidin-1-yl)phenylamino]-4-hydroxybutyric acid
(CHEBI:44860)
has functional parent
butyric acid
(CHEBI:30772)
4-[4-(3,5-dioxohexyl)phenylcarbamoyl]butyric acid
(CHEBI:63773)
has functional parent
butyric acid
(CHEBI:30772)
4-guanidinobutanoic acid
(CHEBI:15728)
has functional parent
butyric acid
(CHEBI:30772)
4-hydroxybutyric acid
(CHEBI:30830)
has functional parent
butyric acid
(CHEBI:30772)
4-methylthio-2-oxobutanoic acid
(CHEBI:33574)
has functional parent
butyric acid
(CHEBI:30772)
4-oxo-4-(2-thienyl)butyric acid
(CHEBI:64434)
has functional parent
butyric acid
(CHEBI:30772)
4-oxo-4-phenylbutyric acid
(CHEBI:64437)
has functional parent
butyric acid
(CHEBI:30772)
4-phenylbutyric acid
(CHEBI:41500)
has functional parent
butyric acid
(CHEBI:30772)
N-(butanoyl)ethanolamine
(CHEBI:85304)
has functional parent
butyric acid
(CHEBI:30772)
N-butanoylserotonin
(CHEBI:134070)
has functional parent
butyric acid
(CHEBI:30772)
N-butyryl-1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphoethanolamine
(CHEBI:85799)
has functional parent
butyric acid
(CHEBI:30772)
O-butanoylcarnitine
(CHEBI:7676)
has functional parent
butyric acid
(CHEBI:30772)
S-butyryl-4ʼ-phosphopantetheine
(CHEBI:132309)
has functional parent
butyric acid
(CHEBI:30772)
D-2,4-diaminobutyric acid
(CHEBI:144635)
has functional parent
butyric acid
(CHEBI:30772)
L-2,4-diaminobutyric acid
(CHEBI:48950)
has functional parent
butyric acid
(CHEBI:30772)
L-2-amino-4-(hydroxymethylphosphinoyl)butanoic acid
(CHEBI:28030)
has functional parent
butyric acid
(CHEBI:30772)
acetoacetic acid
(CHEBI:15344)
has functional parent
butyric acid
(CHEBI:30772)
butyrate ester
(CHEBI:50477)
has functional parent
butyric acid
(CHEBI:30772)
butyryl-CoA
(CHEBI:15517)
has functional parent
butyric acid
(CHEBI:30772)
butyrylglycine
(CHEBI:89963)
has functional parent
butyric acid
(CHEBI:30772)
dibutyrin
(CHEBI:76478)
has functional parent
butyric acid
(CHEBI:30772)
dimethylbutyric acid
(CHEBI:38648)
has functional parent
butyric acid
(CHEBI:30772)
discadenine
(CHEBI:15955)
has functional parent
butyric acid
(CHEBI:30772)
heptafluorobutyric anhydride
(CHEBI:39424)
has functional parent
butyric acid
(CHEBI:30772)
hexyl butyrate
(CHEBI:87559)
has functional parent
butyric acid
(CHEBI:30772)
hydroxybutyric acid
(CHEBI:24684)
has functional parent
butyric acid
(CHEBI:30772)
indole-3-butyric acid
(CHEBI:33070)
has functional parent
butyric acid
(CHEBI:30772)
isooctanediol dibutyrate
(CHEBI:88828)
has functional parent
butyric acid
(CHEBI:30772)
methionine
(CHEBI:16811)
has functional parent
butyric acid
(CHEBI:30772)
methylbutyric acid
(CHEBI:38653)
has functional parent
butyric acid
(CHEBI:30772)
monobutyrin
(CHEBI:76503)
has functional parent
butyric acid
(CHEBI:30772)
perfluorobutyric acid
(CHEBI:39426)
has functional parent
butyric acid
(CHEBI:30772)
perquinoline A
(CHEBI:156391)
has functional parent
butyric acid
(CHEBI:30772)
perquinoline C
(CHEBI:156393)
has functional parent
butyric acid
(CHEBI:30772)
tributyrin
(CHEBI:35020)
has functional parent
butyric acid
(CHEBI:30772)
butyrate
(CHEBI:17968)
is conjugate base of
butyric acid
(CHEBI:30772)
butyryl group
(CHEBI:22972)
is substituent group from
butyric acid
(CHEBI:30772)
|
|
1-butanoic acid
|
HMDB
|
|
1-butyric acid
|
HMDB
|
|
1-propanecarboxylic acid
|
MetaCyc
|
|
4:0
|
ChEBI
|
acide butanoïque
|
IUPAC
|
|
acide butyrique
|
ChEBI
|
|
butanic acid
|
ChEBI
|
|
Butanoate
|
KEGG COMPOUND
|
|
Butanoic acid
|
KEGG COMPOUND
|
|
BUTANOIC ACID
|
PDBeChem
|
|
butoic acid
|
ChEBI
|
Buttersäure
|
ChEBI
|
|
Butyric acid
|
KEGG COMPOUND
|
|
butyric acid
|
IUPAC
|
|
C4:0
|
ChEBI
|
|
CH3‒[CH2]2‒COOH
|
IUPAC
|
|
ethylacetic acid
|
NIST Chemistry WebBook
|
|
n-butanoic acid
|
NIST Chemistry WebBook
|
|
n-butyric acid
|
NIST Chemistry WebBook
|
|
propanecarboxylic acid
|
HMDB
|
|
propylformic acid
|
MetaCyc
|
|
107-92-6
|
CAS Registry Number
|
KEGG COMPOUND
|
|
107-92-6
|
CAS Registry Number
|
ChemIDplus
|
|
107-92-6
|
CAS Registry Number
|
NIST Chemistry WebBook
|
|
26242
|
Gmelin Registry Number
|
Gmelin
|
|
906770
|
Reaxys Registry Number
|
Reaxys
|
Sun S, Li W, Zhang H, Zha L, Xue Y, Wu X, Zou F (2012)
Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells.
Bioscience reports 32, 83-90 [PubMed:21699495]
[show Abstract]
The SOCE (store-operated Ca2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca2+ signalling. In this paper, we provide evidence that butyric acid, a dietary fibre-derived short-chain fatty acid, induces apoptosis of colon cancer cells via SOCE signalling networks. We found that sodium butyrate (NaB) induces Ca2+ release from endoplasmic reticulum, which in turn causes extracellular Ca2+ influx in HCT-116 cells. The Ca2+ release and influx are important, because the addition of chelators, EGTA or BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] respectively blocked NaB-induced apoptosis. Furthermore, down-regulation of STIM1 (stromal interaction molecule 1) by RNA interference or pharmacological blockade of the SOCC (store-operated Ca2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca2+ influx and apoptosis in HCT-116 cells. Thus we conclude that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. This finding provides new insights into how butyric acid suppresses colon carcinogenesis. | Zhang Y, Yu M, Yang ST (2012)
Effects of ptb knockout on butyric acid fermentation by Clostridium tyrobutyricum.
Biotechnology progress 28, 52-59 [PubMed:22038864]
[show Abstract]
Clostridium tyrobutyricum ATCC 25755 is an anaerobic, rod-shaped, gram-positive bacterium that produces butyrate, acetate, hydrogen, and carbon dioxide from various saccharides, including glucose and xylose. Phosphotransbutyrylase (PTB) is a key enzyme in the butyric acid synthesis pathway. In this work, effects of ptb knockout by homologous recombination on metabolic flux and product distribution were investigated. When compared with the wild type, the activities of PTB and butyrate kinase in ptb knockout mutant decreased 76 and 42%, respectively; meanwhile, phosphotransacetylase and acetate kinase increased 7 and 29%, respectively. However, ptb knockout did not significantly reduce butyric acid production from glucose or xylose in batch fermentations. Instead, it increased acetic acid and hydrogen production 33.3-53.8% and ≈ 11%, respectively. Thus, the ptb knockout did increase the carbon flux toward acetate synthesis, resulting in a significant decrease (28-35% reduction) in the butyrate/acetate ratio in ptb mutant fermentations. In addition, the mutant displayed a higher specific growth rate (0.20 h(-1) vs. 0.15 h(-1) on glucose and 0.14 h(-1) vs. 0.10 h(-1) on xylose) and tolerance to butyric acid. Consequently, batch fermentation with the mutant gave higher fermentation rate and productivities (26-48% increase for butyrate, 81-100% increase for acetate, and 38-46% increase for hydrogen). This mutant thus can be used more efficiently than the parental strain in fermentations to produce butyrate, acetate, and hydrogen from glucose and xylose. | Imai K, Yamada K, Tamura M, Ochiai K, Okamoto T (2012)
Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria.
Cellular and molecular life sciences : CMLS 69, 2583-2592 [PubMed:22322557]
[show Abstract]
Latently infected cells harbor human immunodeficiency virus type 1 (HIV-1) proviral DNA copies integrated in heterochromatin, allowing persistence of transcriptionally silent proviruses. It is widely accepted that hypoacetylation of histone proteins by histone deacetylases (HDACs) is involved in maintaining the HIV-1 latency by repressing viral transcription. HIV-1 replication can be induced from latently infected cells by environmental factors, such as inflammation and co-infection with other microbes. It is known that a bacterial metabolite butyric acid inhibits catalytic action of HDAC and induces transcription of silenced genes including HIV-1 provirus. There are a number of such bacteria in gut, vaginal, and oral cavities that produce butyric acid during their anaerobic glycolysis. Since these organs are known to be the major site of HIV-1 transmission and its replication, we explored a possibility that explosive viral replication in these organs could be ascribable to butyric acid produced from anaerobic resident bacteria. In this study, we demonstrate that the culture supernatant of various bacteria producing butyric acid could greatly reactivate the latently-infected HIV-1. These bacteria include Fusobacterium nucleatum (commonly present in oral cavity, and gut), Clostridium cochlearium, Eubacterium multiforme (gut), and Anaerococcus tetradius (vagina). We also clarified that butyric acid in these culture supernatants could induce histone acetylation and HIV-1 replication by inhibiting HDAC. Our observations indicate that butyric acid-producing bacteria could be involved in AIDS progression by reactivating the latent HIV provirus and, subsequently, by eliminating such bacterial infection may contribute to the prevention of the AIDS development and transmission. | Yonezawa H, Osaki T, Hanawa T, Kurata S, Zaman C, Woo TDH, Takahashi M, Matsubara S, Kawakami H, Ochiai K, Kamiya S (2012)
Destructive effects of butyrate on the cell envelope of Helicobacter pylori.
Journal of medical microbiology 61, 582-589 [PubMed:22194341]
[show Abstract]
Helicobacter pylori can be found in the oral cavity and is mostly detected by the use of PCR techniques. Growth of H. pylori is influenced by various factors in the mouth, such as the oral microflora, saliva and other antimicrobial substances, all of which make colonization of the oral cavity by H. pylori difficult. In the present study, we analysed the effect of the cell supernatant of a representative periodontal bacterium Porphyromonas gingivalis on H. pylori and found that the cell supernatant destroyed the H. pylori cell envelope. As P. gingivalis produces butyric acid, we focused our research on the effects of butyrate and found that it significantly inhibited the growth of H. pylori. H. pylori cytoplasmic proteins and DNA were detected in the extracellular environment after treatment with butyrate, suggesting that the integrity of the cell envelope was compromised and indicating that butyrate has a bactericidal effect on H. pylori. In addition, levels of extracellular H. pylori DNA increased following treatment with the cell supernatant of butyric acid-producing bacteria, indicating that the cell supernatant also has a bactericidal effect and that this may be due to its butyric acid content. In conclusion, butyric acid-producing bacteria may play a role in affecting H. pylori colonization of the oral cavity. | Abe K (2012)
Butyric acid induces apoptosis in both human monocytes and lymphocytes equivalently.
Journal of oral science 54, 7-14 [PubMed:22466881]
[show Abstract]
Short-chain fatty acids (SCFAs) are metabolites from anaerobic periodontopathic bacteria that induce apoptosis in immune cells such as lymphocytes, monocytes and macrophages. However, it remains unclear if SCFAs from pathogens induce apoptosis in monocytes/macrophages similarly with lymphocytes. This study investigated whether SCFAs-induced apoptosis is equal among the immunoregulatory cells. Cell apoptosis of the employed human cells was evaluated after treatment with culture supernatants from various periodontopathic bacteria or sodium butyrate. Apoptosis and viability were determined by detection of DNA fragmentation and using an MTS assay kit, respectively. Porphyromonas gingivalis and Fusobacterium nucleatum culture filtrates strongly induced apoptosis whereas Prevotella nigrescens and Prevotella intermedia culture filtrates failed to induce apoptosis in the THP-1 and U937 human monocyte and macrophage cell lines. Healthy gingival fibroblasts and oral epithelial cells were resistant to all the culture filtrates. Gas-liquid chromatography detected butyric acid in P. gingivalis (21.0-34.0 mM) and F. nucleatum (36.0 mM) in culture filtrates, whereas, only trace levels were seen in P. nigrescens and P. intermedia. These results suggest that butyric acid produced by periodontopathic bacteria severely damages immunoregulatory cells in a consistent manner and, likewise, could be involved in mediating periodontal chronic inflammation. | Fu B, Zhang J, Fan J, Wang J, Liu H (2012)
Control of C/N ratio for butyric acid production from textile wastewater sludge by anaerobic digestion.
Water science and technology : a journal of the International Association on Water Pollution Research 65, 883-889 [PubMed:22339023]
[show Abstract]
Increasing textile wastewaters and their biotreatment byproduct-waste activated sludge are serious pollution problems. Butyric acid production from textile wastewater sludge by anaerobic digestion at different C/N ratios was investigated. Adding starch to textile wastewater sludge with a C/N ratio of 30 increased the butyric acid concentration and percentage accounting for total volatile fatty acids (TVFAs) to 21.42 g/L and 81.5%, respectively, as compared with 21.42 g/L and 10.6% of textile wastewater sludge alone. The maximum butyric acid yield (0.45 g/g VS), conversion rate (0.74 g/g VS(digest)) and production rate (2.25 g/L d) was achieved at a C/N ratio of 30. The biological toxicity of textile wastewater sludge also significantly decreased after the anaerobic digestion. The study indicated that the anaerobic co-digestion of textile wastewater sludge and carbohydrate-rich waste with appropriate C/N ratio is possible for butyric acid production. | Patel VB, Yu Y, Das JK, Patel BB, Majumdar AP (2009)
Schlafen-3: a novel regulator of intestinal differentiation.
Biochemical and biophysical research communications 388, 752-756 [PubMed:19703412]
[show Abstract]
Schlafen-3 (Slfn-3), a novel gene, has been shown to be a negative regulator of proliferation. The current investigation was undertaken to determine whether Slfn-3 might play a role in regulating cellular differentiation. Butyric acid, a short chain fatty acid, which induced differentiation of intestinal cells as evidenced by increased alkaline phosphatase (ALP) activity in the rat small intestinal IEC-6 cells, also produced a marked increase in Slfn-3 expression. Furthermore, overexpression of Slfn-3 caused stimulation of ALP activity in IEC-6 cells, which was exacerbated by butyrate. On the other hand, downregulation of Slfn-3 by slfn-3-si-RNA greatly attenuated the butyrate-mediated induction of differentiation of IEC-6 cells. Additionally, we observed that increased expression of Slfn-3 in colon cancer HCT-116 cells stimulated TGF-beta expression and modulated expression of its downstream effectors as evidenced by increased expression of p27kip1 and downregulation of CDK-2. In addition, Slfn-3 increases E-cadherin expression but downregulates beta-catenin. In conclusion, our data show that Slfn-3 plays a critical role in regulating intestinal mucosal differentiation. Furthermore our data also show that TGF-beta signaling pathway plays an important role in mediating slfn-3 induced differentiation. | Lin CN, Wu SY, Chang JS, Chang JS (2009)
Biohydrogen production in a three-phase fluidized bed bioreactor using sewage sludge immobilized by ethylene-vinyl acetate copolymer.
Bioresource technology 100, 3298-3301 [PubMed:19318247]
[show Abstract]
Ethylene-vinyl acetate (EVA) copolymer was used to immobilize H(2)-producing sewage sludge for H(2) production in a three-phase fluidized bed reactor (FBR). The FBR with an immobilized cell packing ratio of 10% (v/v) and a liquid recycle rate of 5l/min (23% bed expansion) was optimal for dark H(2) fermentation. The performance of the FBR reactor fed with sucrose-based synthetic medium was examined under various sucrose concentration (C(so)) and hydraulic retention time (HRT). The best volumetric H(2) production rate of 1.80+/-0.02 H(2) l/h/l occurred at C(so)=40 g COD/l and 2h HRT, while the optimal H(2) yield (4.26+/-0.04 mol H(2)/mol sucrose) was obtained at C(so)=20 g COD/l and 6h HRT. The H(2) content in the biogas was stably maintained at 40% or above. The primary soluble metabolites were butyric acid and acetic acid, as both products together accounted for 74-83% of total soluble microbial products formed during dark H(2) fermentation. | Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J (2009)
Butyrate improves insulin sensitivity and increases energy expenditure in mice.
Diabetes 58, 1509-1517 [PubMed:19366864]
[show Abstract]
ObjectiveWe examined the role of butyric acid, a short-chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high-fat diet.Research design and methodsIn dietary-obese C57BL/6J mice, sodium butyrate was administrated through diet supplementation at 5% wt/wt in the high-fat diet. Insulin sensitivity was examined with insulin tolerance testing and homeostasis model assessment for insulin resistance. Energy metabolism was monitored in a metabolic chamber. Mitochondrial function was investigated in brown adipocytes and skeletal muscle in the mice.ResultsOn the high-fat diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice. Fasting blood glucose, fasting insulin, and insulin tolerance were all preserved in the treated mice. Body fat content was maintained at 10% without a reduction in food intake. Adaptive thermogenesis and fatty acid oxidation were enhanced. An increase in mitochondrial function and biogenesis was observed in skeletal muscle and brown fat. The type I fiber was enriched in skeletal muscle. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression was elevated at mRNA and protein levels. AMP kinase and p38 activities were elevated. In the obese mice, supplementation of butyrate led to an increase in insulin sensitivity and a reduction in adiposity.ConclusionsDietary supplementation of butyrate can prevent and treat diet-induced insulin resistance in mouse. The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondria function. | Orchel A, Dzierzewicz Z, Parfiniewicz B, Weglarz L, Wilczok T (2005)
Butyrate-induced differentiation of colon cancer cells is PKC and JNK dependent.
Digestive diseases and sciences 50, 490-498 [PubMed:15810631]
[show Abstract]
Butyric acid, a short-chain fatty acid physiologically present in human large gut, is derived from bacterial fermentation of complex carbohydrates. It has been shown to reduce the growth and motility of colon cancer cell lines and to induce cell differentiation and apoptosis. Apoptosis is considered a result of normal colonocyte terminal differentiation in vivo. The aim of this study was to characterize the cellular mechanisms regulating differentiation of colon cancer cells stimulated with sodium butyrate (NaB). The two human colon cancer cell lines Caco-2 and HT-29 were treated with NaB at physiologically relevant concentrations. Alkaline phosphatase (ALP) activity, a marker of colonocyte differentiation, was increased 48 hr after treatment with 1 mM NaB. Higher doses of NaB (5 and 10 mM) induced apoptosis of the cells and failed to stimulate the colonocyte differentiation. Therefore, we assumed that butyrate augments cell differentiation and induces apoptosis, acting via various intracellular mechanisms, and butyrate-mediated programmed cell death cannot be considered a consequence of colonocyte terminal differentiation. The effect of NaB on ALP activity was significantly attenuated in the presence of inhibitors of protein kinase C and JNK. Inhibition of MEK-ERK signal transduction pathways augmented the impact of butyrate on colonocyte differentiation. These results suggest that butyrate could influence the colonocyte differentiation via modulation of the activity of cellular protein kinases and signal transduction. | Komata T, Kanzawa T, Nashimoto T, Aoki H, Endo S, Kon T, Takahashi H, Kondo S, Tanaka R (2005)
Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis in human malignant glioma cells.
International journal of oncology 26, 1345-1352 [PubMed:15809727]
[show Abstract]
Histone deacetylase (HDAC) inhibitors have both apoptotic and differentiating effects on various tumor cells. However, the mechanisms underlying the effect of HDAC inhibitors remain unclear. In this study, we investigated the function of anti-proliferative effects of HDAC inhibitors, N-butyric acid and trichostatin A, on human malignant glioma cell lines, U251-MG and D54. MTT assay showed a dose-dependent inhibition of cellular proliferation in both cell lines. Cell cycle analysis revealed increased sub-G1 population in both lines, and G1 arrest only in U251-MG cells. Induction of apoptosis was also supported by the occurrence of DNA fragmentation in tumor cells treated with HDAC inhibitors. Furthermore, caspase inhibition assay indicated that HDAC inhibitor-induced apoptosis was caspase-dependent. Neither mitochondrial membrane potential nor the expression of caspase-9 was changed by treatment with HDAC inhibitors, suggesting the possibility that HDAC inhibitor-induced apoptosis was not mediated by the mitochondrial cell death pathway. On the other hand, immunoblot assay confirmed increased expression of caspase-8 in both lines, and elevation of p21 but not p27 protein in U251-MG cells following HDAC inhibitor treatment. Taken together, the HDAC inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis with or without p21-mediated G1 arrest in human malignant glioma cells. | Li QQ, Meng HX, Gao XJ, Wang ZH (2005)
[Analysis of volatile fatty acids in gingival crevicular fluid of patients with chronic periodontitis].
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 40, 208-210 [PubMed:15938880]
[show Abstract]
ObjectiveTo investigate the volatile fatty acids in gingival crevicular fluid (GCF) and to analyze the relationship between the levels of the volatile fatty acids and chronic periodontitis.MethodsGCF samples taken from 37 patients with chronic periodontitis and 16 volunteers with healthy periodontal status were analyzed by capillary electrophoresis.ResultsThe detection frequencies and concentrations of succinic acid, butyric acid and valeric acid were significantly higher in GCF of chronic periodontitis than in that of healthy group. The detection frequencies of propionic acid had no statistic difference between the two groups, but the concentrations of it was significantly higher in inflammation group. We also found that the concentrations of succinic acid, propionic acid and butyric acid were significantly lower in shallow pockets than that in deep pockets.ConclusionsThe volatile fatty acids, especially succinic acid, propionic acid, butyric acid and valeric acid were associated significantly with the severity and inflammation of periodontal disease. The levels of succinic acid, propionic acid and butyric acid in GCF were related to pocket depth. | Lin J (2004)
Too much short chain fatty acids cause neonatal necrotizing enterocolitis.
Medical hypotheses 62, 291-293 [PubMed:14962641]
[show Abstract]
Nenatal necrotizing enterocolitis (NEC) is a disease mainly affects premature infants. It is well known that prematurity, enteral formula feeding, and bacterial colonization are three major risk factors for NEC. Acetic acid, propionic acid and butyric acid are short chain fatty acids (SCFAs), which are produced mainly in the colon by bacterial fermentation of undigested carbohydrates. Although luminal production of modest quantities of SCFAs is essential for normal colonic mucosal function, excessive production/accumulation of SCFAs may arise in premature infants due to increased luminal carbohydrates malabsorption and poor gastrointestinal motility, and may have deleterious effects on mucosal integrity. Therefore, it is proposed that too much luminal short chain fatty acids cause neonatal NEC. | Orchel A, Molin I, Dzierzewicz Z, Latocha M, Weglarz L, Wilczok T (2003)
Quantification of p21 gene expression in Caco-2 cells treated with sodium butyrate using real-time reverse transcription-PCR (RT-PCR) assay.
Acta poloniae pharmaceutica 60, 103-105 [PubMed:13678314]
[show Abstract]
Butyric acid, a short chain fatty-acid derived from bacterial fermentation of complex carbohydrates in the large intestine has been shown to be a growth inhibitory in many colon cancer cell lines. Butyrate induced inhibition of cellular proliferation is considered to result from the induction of P21 gene expression through the activation of this gene transcription. P21 is an inhibitor of cyclin-dependent protein kinases that are required for the cells to enter the DNA synthesis phase. In the present study the kinetics of the changes of the P21 transcription in Caco-2 colon adenocarcinoma cells treated with various concentrations of sodium butyrate was determined using a novel real-time quantitative RT-PCR (TaqMan) technique. Beta-actin mRNA and GAPDH mRNA levels were used as the endogenous references. Colonocytes were incubated with sodium butyrate at concentrations of 5 mM, 10 mM and 20 mM for 3, 6, 12, 24 and 48 h. The results of this study indicated that butyrate strongly induced P21 gene expression as early as 3 h after treatment. Characteristic patterns of time-dependent changes of the target gene expression were observed. The increases in P21 mRNA level were generally more pronounced at higher butyrate concentrations. Because Caco-2 cells are lacking the wild allele of the P53 gene, the present results support the hypothesis that butyrate induces P21 gene expression by P53-independent mechanism. | Mentschel J, Leiser R, Mülling C, Pfarrer C, Claus R (2001)
Butyric acid stimulates rumen mucosa development in the calf mainly by a reduction of apoptosis.
Archiv fur Tierernahrung 55, 85-102 [PubMed:12068484]
[show Abstract]
In ruminants the stimulation of papillar growth by butyric acid is well described but effects on mitosis and apoptosis are not known. To clarify the effect of short chain fatty acids three groups of three calves received a basic ration of 100 g hay per day for 6 weeks and additionally milk replacer. From these, two groups were fed with increasing amounts of the salts of either propionic acid (53 to 390 g) or butyric acid up to (54 to 326 g). The control group instead received an additional isocaloric amount of milk replacer. Mitosis was characterized by Ki67 immunoreactivity, apoptosis by a modified TUNEL assay and by electron microscopy. The feeding regimes led to significant differences of papillar length, increasing from 1.0 mm (controls) to 2.2 mm (propionic acid) and 4 mm (butyric acid). This enlargement was partly explained by an increased mitotic rate for the two fatty acid groups. The difference between the fatty acid groups was mainly explained by different apoptotic rates which were only one third for butyric acid compared to propionic acid (P < 0.001). In conclusion, butyric acid is a specific inhibitor of ruminal apoptosis in vivo. | Zhang X, Dong FC, Gao JF, Song CP (2001)
Hydrogen peroxide-induced changes in intracellular pH of guard cells precede stomatal closure.
Cell research 11, 37-43 [PubMed:11305323]
[show Abstract]
Epidermal bioassay demonstrated that benzylamine, a membrane-permeable weak base, can mimick hydrogen peroxide (H2O2) to induce stomatal closure, and butyric acid, a membrane-permeable weak acid, can partly abolish the H2O2-induced stomatal closure. Confocal pH mapping with the probe 5-(and-6)-carboxy seminaphthorhodafluor-1-acetoxymethylester (SNARF-1-AM) revealed that H2O2 leads to rapid changes in cytoplasmic and vacuolar pH in guard cells of Vicia faba L, i. e. alkalinization of cytoplasmic areas occur red in parallel with a decrease of the vacuolar pH, and that butyric acid pretreatment can abolish alkalinization of cytoplasmic areas and acidification of vacuolar areas of guard cells challenged with H2O2. These results imply that the alkalinization of cytoplasm via efflux of cytosol protons into the vacuole in guard cells challenged with H2O2 is important at an early stage in the signal cascade leading to stomatal closure. | Kurita-Ochiai T, Ochiai K, Fukushima K (2001)
Butyric acid-induced T-cell apoptosis is mediated by caspase-8 and -9 activation in a Fas-independent manner.
Clinical and diagnostic laboratory immunology 8, 325-332 [PubMed:11238216]
[show Abstract]
Our previous study demonstrated that butyric acid, an extracellular metabolite of periodontopathic bacteria, induced apoptosis in murine thymocytes, splenic T cells, and human Jurkat cells. In this study, we examined whether CD95 ligand-receptor interaction is involved in butyric acid-induced T-cell apoptosis. Flow cytometry analysis indicated that expression of Fas in Jurkat and T cells from peripheral blood mononuclear cells was not affected by butyric acid treatment. Furthermore, the expression of Fas and FasL protein in Western blotting was not affected by butyric acid treatment. Coincubation with blocking anti-Fas antibodies prevented Fas-induced apoptosis but not butyric acid-induced apoptosis. Anti-FasL antibodies also did not prevent butyric acid-induced apoptosis at any dose examined. Although cytotoxic anti-Fas antibody affected butyric acid-induced apoptosis, a synergistic effect was not seen. Time-dependent activation of caspase-8 and -9 was recognized in butyric acid- as well as Fas-mediated apoptosis. IETD-CHO and LEHD-CHO, specific inhibitors of caspase-8 and -9, respectively, completely blocked Fas-mediated apoptosis and partially prevented butyric acid-induced apoptosis. These results suggest that the Fas-FasL interaction is not involved in butyric acid-induced apoptosis and that caspase-8 and -9-dependent apoptosis plays an important role in butyric acid-induced apoptosis, as well as Fas-induced apoptosis. | Mandal M, Olson DJ, Sharma T, Vadlamudi RK, Kumar R (2001)
Butyric acid induces apoptosis by up-regulating Bax expression via stimulation of the c-Jun N-terminal kinase/activation protein-1 pathway in human colon cancer cells.
Gastroenterology 120, 71-78 [PubMed:11208715]
[show Abstract]
Background & aimsThe colonic epithelial cells near the top of the crypt have been shown to undergo apoptosis. Because butyric acid (BA) is the major short-chain fatty acid produced by fermentation of dietary fiber in the large bowel, it may be an important regulator of apoptosis in colorectal cancer. We investigated which signaling pathway is triggered by BA to undergo apoptosis in human colorectal cancer cells.MethodsHuman DiFi and FET colorectal cells were treated with BA to undergo apoptosis and were assayed for activation of c-Jun N-terminal kinase (JNK), transcription factor activation protein 1 (AP1) and NF-kappaB, and the proapoptotic molecule Bax. The contribution of specific pathways was assessed by examining the effects of dominant-negative mutants of JNK/AP1 or NF-kappaB on BA-induced Bax expression and apoptosis.ResultsBA-mediated DNA fragmentation and Bax induction were preceded by early stimulation of JNK, and the DNA-binding activities of AP1 and NF-kappaB. BA-induced enhancement of DNA fragmentation and stimulation of Bax promoter activity were blocked by the expression of dominant-negative mutants of JNK1 or AP1 but not NF-kappaB.ConclusionsThese findings suggest that apoptosis triggered by BA involves transcriptional stimulation of the Bax gene via activation of the JNK/AP1 pathway in colonic epithelial cells. | Kurita-Ochiai T, Ochiai K, Fukushima K (2000)
Butyric-acid-induced apoptosis in murine thymocytes and splenic T- and B-cells occurs in the absence of p53.
Journal of dental research 79, 1948-1954 [PubMed:11201044]
[show Abstract]
Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine thymocytes, splenic T-cells, and human Jurkat T-cells. The present study examines the contributions of apoptosis-related proteins (Bcl-2, Bcl-XL, Bax, and p21WAF1/CIP1) in the regulation of T-cell death induced by butyric acid, using p53 knock-out (p53-/-) and wild-type (p53+/+) mice. The results of a DNA fragmentation assay indicated that thymocytes, splenic T-cells, and B-cells from p53-/- mice were susceptible to butyric-acid-induced apoptosis to a degree similar to those from p53+/+ mice. Moreover, butyric acid significantly induced apoptosis in lymphocytes from both p53+/+ and p53-/- mice in a concentration- and time-dependent fashion. Experiments with fractionated subpopulations of splenic T-cells revealed that DNA fragmentation was equally observed in CD4+ and CD8+ splenic T-cells from both p53+/+ and p53-/- lymphocytes. Activation of caspase-3, caspase-6, and caspase-8, but not of caspase-1, in butyric-acid-induced T-cell apoptosis occurred regardless of the presence of p53. Western blotting analysis of splenic T-cells showed that butyric acid treatment decreased Bcl-2 and Bcl-XL expressions in p53+/+ and p53-/- cells. Splenic T-cells had barely detectable Bax and p21WAF1/CIP1, regardless of whether butyric acid and/or p53 was present. These results suggest that butyric-acid-mediated apoptosis of murine T-cells takes place via a pathway that is independent of p53, and is followed by the p53-regulated proteins Bax and p21WAF1/CIP1, which lower the levels of the apoptosis antagonists Bcl-2 and Bcl-XL in cells. | Nudelman A, Rephaeli A (2000)
Novel mutual prodrug of retinoic and butyric acids with enhanced anticancer activity.
Journal of medicinal chemistry 43, 2962-2966 (Source: ChEMBL) [PubMed:10956204]
[show Abstract]
Acyloxylalkyl esters of retinoic acid and small carboxylic acids (C3-5) were evaluated for anticancer activity. The derivative of butyric acid (BA) and all-trans-retinoic acid (ATRA)-retinoyloxymethyl butyrate (RN1)-acting as a mutual prodrug was a more potent inducer of cancer cell differentiation and inhibitor of proliferation than the parent acids. ED50 of RN1 for differentiation induction in HL-60 was over 40-fold lower than that of ATRA. The differentiating activity of ATRA compared to that of the acyloxylalkyl esters derived from butyric (RN1), propionic (RN2), isobutyric (RN3), and pivalic (RN4) acids was found to be: RN1 > RN2 > RN3 > ATRA approximately RN4. This observation implies that the activity of the prodrugs depends on the specific acyl fragment attached to the retinoyl moiety, and the butyroyl fragment conferred the highest potency. The IC50 values for inhibition of Lewis lung (3LLD122) and pancreatic (PaCa2) carcinoma cell line colony formation elicited by RN1 were significantly higher than those of ATRA. In addition to its superiority over ATRA or BA as growth inhibitors of the above cell lines, RN1 was also able to overcome the resistance to ATRA in 3LLD122 cells. | Russo GL, Della Pietra V, Mercurio C, Palumbo R, Iacomino G, Russo M, Tosto M, Zappia V (1999)
Protective effects of butyric acid in colon cancer.
Advances in experimental medicine and biology 472, 131-147 [PubMed:10736622] | Nudelman A, Ruse M, Aviram A, Rabizadeh E, Shaklai M, Zimrah Y, Rephaeli A (1992)
Novel anticancer prodrugs of butyric acid. 2.
Journal of medicinal chemistry 35, 687-694 (Source: ChEMBL) [PubMed:1542095]
[show Abstract]
The antitumor activity of novel prodrugs butyric acid was examined. The in vitro effect of the compounds on induction of cytodifferentiation and on inhibition of proliferation and clonogenicity showed that (pivaloyloxy)methyl butyrate (1a) (labeled AN-9) was the most active agent. SAR's suggested that its activity stemmed from hydrolytically released butyric acid. In vivo, 1a displayed antitumor activity in B16F0 melanoma primary cancer model, manifested by a significant increase in the life span of the treated animals. Murine lung tumor burden, induced by injection of the highly metastatic melanoma cells (B16F10.9), was decreased by 1a. It also displayed a significant therapeutic activity against spontaneous metastases which were induced by 3LL Lewis lung carcinoma cells. Moreover, 1a has the advantage of low toxicity, with an acute LD50 = 1.36 +/- 0.1 g/kg (n = 5). These results suggest that 1a is a potential antineoplastic agent. |
|
2011-03-29
