title: 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.
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.
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Tiwari
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, India.
authors.forename: Satya
authors.initials: S
authors.lastname: Sahay
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, India.
authors.forename: Manuraj
authors.initials: M
authors.lastname: Pandey
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, India; Pathology Division, National Institute of Nutrition, Hyderabad, India.
authors.forename: Syed S Y H
authors.initials: SS
authors.lastname: Qadri
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, India. Electronic address: krishnag522@yahoo.co.in.
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Gupta
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000494:pharmacology*; D020148:Butyric Acid / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D003575:Cytochromes c1 / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005937:Glucaric Acid / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D001688:Biological Products; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D020148:Butyric Acid; D009536:Niacinamide; D015127:9,10-Dimethyl-1,2-benzanthracene; D003575:Cytochromes c1; D020169:Caspases; D005937:Glucaric Acid
keywords: Apoptosis; Chemoprevention; Multiagents; Skin tumor