Modulation of p21, DAPK1 and COX-2 during the DMBA/TPA-induced mouse skin tumorigenesis and its prevention by phytic acid

Chhaya Pandey, Rashmi Arnold, Rahasya Mani Mishra


Chemoprevention by naturally occurring agents is gaining much attention as a newer
dimension in the management of cancer. Many naturally occurring agents have shown cancer
chemopreventive potential in a variety of bioassay systems and animal models, having
relevance to human disease. Phytic acid or Inositol hexaphosphate (IP6), an antioxidant, is a
naturally occurring polyphosphorylated carbohydrate that has shown a strong anticancer
activity in several experimental models. We assessed the protective effects of Phytic acid
against the 7, 12-dimethylbenz [a] anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13-
acetate (TPA) induced mouse skin tumorigenesis at 4 and 16 weeks, the time before and after
the tumor development. At molecular level we studied expression and promoter CpG
methylation status of p21, DAPK1 and COX-2. Our data suggests exposure of DMBA/TPA
methylated the promoter region of p21 and DAPK1 genes in time dependent manner that
could be the cause of down regulation of their expression with time, which were reversed by
administration of phytic acid. But we did not observe methylation in COX-2 whereas
upregulation of COX-2 was observed at protein level in mice treated with DMBA followed
by TPA in time dependent manner. Administration of phytic acid prevented theses
DMBA/TPA induced molecular changes. Study provides a rationale for cancer
chemoprevention by natural occurring compounds like Phytic acid.


DMBA/TPA, Skin tumorigenesis, Promoter methylation, Chemoprevention.

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