Suppression of DMBA-induced mouse skin tumor development by inositol hexaphosphate and its mode of action.
Inositol hexaphosphate (IP6) or phytic acid, contained in most mammalian cells, has been shown to have anticancer and anti-cell-proliferative effects in several experimental models of carcinogenesis. We investigated the effect of topical application of IP6 on 7,12-dimethylbenzanthracene (DMBA)-induced complete carcinogenesis and on selective critical events of proliferation, differentiation, or apoptosis after DMBA exposure. IP6 inhibited skin tumor development significantly in a dose-dependent manner. IP6 induced the DMBA-inhibited transglutaminase activity. DNA synthesis, as determined by [3H]thymidine incorporation, was suppressed by IP6 in a dose-dependent manner. IP6 also inhibited thymidine kinase enzyme, which is responsible for [3H]thymidine incorporation into DNA. Our results show that topical application of IP6 inhibits DMBA-induced mouse skin tumor development and that IP6 exerts its tumor inhibitory effect probably by modulating proliferation, differentiation, or apoptosis. It seems that IP6 is an effective and potential chemopreventive agent for management of skin tumorigenesis.
Gupta
Krishna P
KP
Environmental Carcinogenesis Division, Industrial Toxicology Research Center, M G Marg, Lucknow-226001, India. krishnag2@rediffmail.com
Singh
Jaya
J
Bharathi
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage*; D000818:Animals; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000201:enzymology / Q000473:pathology; D005260:Female; D051379:Mice; D010833:Phytic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013937:Thymidine Kinase / Q000187:drug effects; D011503:Transglutaminases / Q000187:drug effects
D015127:9,10-Dimethyl-1,2-benzanthracene; D010833:Phytic Acid; D004247:DNA; D011503:Transglutaminases; D013937:Thymidine Kinase