title: IP6 in treatment of liver cancer. I. IP6 inhibits growth and reverses transformed phenotype in HepG2 human liver cancer cell line.
abstract: Hepatocellular carcinoma (HCC) is a common tumor world-wide with extremely poor prognosis. Recent studies have shown that inositol hexaphosphate (IP6), a naturally occurring carbohydrate, has novel anti-cancer function in various in vitro and in vivo models. The aim of this study was to assess whether IP6 could inhibit the growth of human hepatocellular carcinoma. We treated HepG2, a human liver cancer cell line in vitro with IP6 and evaluated its effect on growth and differentiation. IP6 treatment of HepG2 cells caused a dose-dependent growth inhibition. Compared to other cancer cell lines, HepG2 cells were quite sensitive to IP6, IC50 (50% inhibition of cell growth) of IP6 being < 1.0 mM (0.338 mM). Treatment with IP6 decreased the ability of HepG2 cells to form colonies, as assessed in the plating efficiency assay. Morphological changes induced by IP6 were consistent with differentiation of HepG2 cells. Exposure of HepG2 cells to IP6 drastically decreased the rate of production of alpha-fetoprotein (AFP), a tumor marker of HCC, indicating also that IP6 treatment leads to differentiation of malignant liver cells. Further, IP6 treatment caused a decreased expression of mutant p53 protein in HepG2 cells, with no significant change in the expression of wild-type p53. The expression of p21WAF1 protein was increased by 1.5 fold, as determined by immunocytochemical staining and ELISA assay. These data demonstrate that IP6 inhibits the growth, and induces differentiation, and a less aggressive phenotype of HepG2 cells, suggesting a role of IP6 in the treatment of HCC.
authors.affiliation: Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: I
authors.initials: I
authors.lastname: Vucenik
authors.forename: K
authors.initials: K
authors.lastname: Tantivejkul
authors.forename: Z S
authors.initials: ZS
authors.lastname: Zhang
authors.forename: K E
authors.initials: KE
authors.lastname: Cole
authors.forename: I
authors.initials: I
authors.lastname: Saied
authors.forename: A M
authors.initials: AM
authors.lastname: Shamsuddin
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D018197:Hepatoblastoma / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D010641:Phenotype; D010833:Phytic Acid / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins; D010833:Phytic Acid