NOVEL ANTICANCER FUNCTION OF INOSITOL HEXAPHOSPHATE - INHIBITION OF HUMAN RHABDOMYOSARCOMA IN-VITRO AND IN-VIVO

Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylat ed carbohydrate that has been shown to suppress the growth of epitheli al cancers, including those of breast and colon. The objective of this study was to investigate whether IP6 inhibits growth of rhabdomyosarc oma (RMS), a tumor of mesenchymal origin, which is the most common sof t tissue sarcoma in children. We performed both in vitro and in vivo s tudies to evaluate the effect of IP6 on human RD cells growth. Our res ults show that IP6 suppresses growth of rhabdomyosarcoma cell line (RD ) in vitro in a dose-dependent fashion. A 50% inhibition of cell growt h (IC50) was induced by < 1.0 mM IP6. However, the removal of IP6 from the media, after 72 hours of treatment, allowed cells to recover thei r logarithmic growth. Exposure of RD cells to IP6 led to differentiati on; cells became larger with abundant cytoplasm, expressing higher lev els of muscle-specific actin. Consistent with in vitro observation, IP 6 suppressed RD cell growth in vivo, in a xenografted nude mice model. When compared to controls, IP6-treated mice produced a 25 fold smalle r tumors (p=0.008), as observed after a two week treatment, In a secon d experiment, wherein the treatment period was extended to five weeks, a 49 fold (p=0.001) reduction in tumor size was observed in mice trea ted with IP6. Histologically no evidence of tumor cell necrosis was ob served These data suggest a potential usefulness of this cytostatic, a nd non-cytotoxic, compound in novel therapeutic strategies for these t ypes of tumor.