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 present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (< 1000 Dalton) of skeletal muscle cell conditioned medium (muscle factor-MF), markedly inhibits the proliferation of carcinoma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic effect on tumor cell growth and arrests the cells in the G0/G1 of the cell cycle. However, normal cell proliferation, such as bone marrow and fibroblasts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mice. The administration of MF to mice inoculated intravenously with melanoma (B16-F10) or sarcoma (MCA-105) cells, resulted in a statistically significant 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 was amputated. A prolonged survival time was observed in the MF treated groups. Since the MF stimulated bone marrow cell proliferation in vitro, we decided to test its efficacy as an inhibitor of the myelotoxic effect exerted by chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutrophils compared with the decline in these parameters after administration of chemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tumor 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.
Bar-Yehuda
S
S
Laboratory of Clinical and Tumor Immunology, The Felsenstein Medical Research Center, Tel-Aviv University, Rabin Medical Center, Petach-Tikva, Israel.
Farbstein
T
T
Barer
F
F
Ohana
G
G
Fishman
P
P
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D008175:Lung Neoplasms / Q000188:drug therapy / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology*
D000970:Antineoplastic Agents; D009124:Muscle Proteins