Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice

Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The presen t study focuses on small molecules produced and secreted by muscle cells wh ich possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (< 1000 Dalton) of skeletal muscle cell conditio ned medium (muscle factor-MF), markedly inhibits the proliferation of carci noma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic e ffect on tumor cell growth and arrests the cells in the G0/G1 of the cell c ycle. However, normal cell proliferation, such as bone marrow and fibroblas ts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mi ce. The administration of MF to mice inoculated intravenously with melanoma (B16-F10) or sarcoma (MCA-105) cells, resulted in a statistically signific ant inhibition of metastatic lung foci. In a different model, melanoma was induced in the foot pad and after development of a local lesion, the leg wa s amputated. A prolonged survival time was observed in the MF treated group s. Since the MF stimulated bone marrow cell proliferation in vitro, we deci ded to test its efficacy as an inhibitor of the myelotoxic effect exerted b y chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutroph ils compared with the decline in these parameters after administration of c hemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tu mor and chemoprotective effect when given orally. It can be concluded that it is bioavailable and is not biodegradable in the digestive system. MF may be considered as a potential therapy for the prevention of tumor spread.