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Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events
- Source :
- Chemico-Biological Interactions. 226:1-11
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development.
- Subjects :
- Cyclin-Dependent Kinase Inhibitor p21
Niacinamide
Cytoplasm
congenital, hereditary, and neonatal diseases and abnormalities
Programmed cell death
Skin Neoplasms
Carcinogenesis
9,10-Dimethyl-1,2-benzanthracene
DMBA
Calcium glucarate
Apoptosis
Cytochromes c1
Toxicology
Glucaric Acid
Mice
chemistry.chemical_compound
Downregulation and upregulation
Animals
Anticarcinogenic Agents
Drug Interactions
RNA, Messenger
bcl-2-Associated X Protein
Biological Products
Nicotinamide
biology
Chemistry
7,12-Dimethylbenz[a]anthracene
Cytochrome c
General Medicine
Mitochondria
Enzyme Activation
Gene Expression Regulation, Neoplastic
Apoptotic Protease-Activating Factor 1
Proto-Oncogene Proteins c-bcl-2
Caspases
Cancer research
biology.protein
Butyric Acid
Female
Subjects
Details
- ISSN :
- 00092797
- Volume :
- 226
- Database :
- OpenAIRE
- Journal :
- Chemico-Biological Interactions
- Accession number :
- edsair.doi.dedup.....f879aef229463e77fd54a29c36459c4e