Inositol hexaphosphate induces apoptosis by coordinative modulation of P53, Bcl-2 and sequential activation of caspases in 7,12 dimethylbenz[a]anthracene exposed mouse epidermis.
Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds, and soybean. Anticancer effects of IP6 have been demonstrated in different experimental models. Besides reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in restoring the normal phenotype. Exogenously administered IP6 is rapidly taken into the cells and dephosphorylated to lower-phosphate, inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties could also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. The present study deals with the effect of topical application of IP6 on some of the selective and critical events of apoptosis in DMBA exposed mouse epidermis. IP6 showed an inhibition of DMBA-induced mutant (mt) p53 expression. Similarly, DMBA induced over expression of Bcl-2 was also reversed by topical treatment of IP6. In addition to the modulation of mt p53 and Bcl-2 expressions, IP6 brought the DMBA-inhibited activity of caspases back to the normal or induced it above the normal levels. The effects of IP6 appeared to be the function of its dose and the duration of its exposure. These results suggested that topically applied IP6 directly induces apoptotic machinery by modulating the expression of mt p53, Bcl-2, and caspase activity.
Singh
Jaya
J
Environmental Carcinogenesis Division, Industrial Toxicology Research Center, Mahatma Gandhi Marg, Lucknow-226001, India.
Gupta
Krishna P
KP
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism*; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D010833:Phytic Acid / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000970:Antineoplastic Agents; D002273:Carcinogens; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D010833:Phytic Acid; D020169:Caspases