Up-regulation of the tumor suppressor gene P53 and WAF1 gene by IP6 in HPG2 human hepatocellular carcinoma cell line

ABSTRACT

Inositol hexaphosphate [InsP6 or IP6] is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. IP6 exerts its effects on the body by controlling cell division. It reduces the rate of cellular proliferation, both in vivo and in vitro, and has exhibited an ability to reduce DNA synthesis and also causes differentiation of various cell lines, including HT-29 human colon carcinoma cell. We hypothesize that the tumor suppressor genes such as p53 and WAF1 may be involved in mediating the antineoplastic action of IP6. p53 acts as a molecular policeman preventing propagation of genetically damaged cells; it causes the cells to arrest in the G1 phase of cell cycle, and regulates the level of p21 wafl which acts as a growth inhibitor. We therefore investigated the effects of IP6 on the expression of p53 and WAF1/p21 in HP-G2 human hepatocellular carcinoma by immunocytochemistry. Our immunocytochemical studies with anti p53 antibodies [wild type-PAb246 and Pab 1620] and anti p21 wafl [EA10] antibodies demonstrated an increased level of p53 and p21 wafl after 3 and 6 days of treatment with 3.3 and 5 mM and 8 mM IP6. This increase was dose-dependent and a definite time-dependent increase was not observed. These data demonstrate that IP6 up-regulates the expression of the tumor suppressor gene p53 and p21waf1 gene and their modulation may be one of the mechanisms of the antineoplastic action of IP6 since loss of p53 function enhances cancer cells resistance to chemotherapeutic agents, the stimulating function of IP6 on p53 makes it an attractive adjuvant chemotherapeutic agent as well