Selective effect of trichotecolone on hemopoietic tumor cells

The effects of trichothecolone, a mycotoxin produced by the mould Trichothecium roseum, were tested at graded concentrations (50 to 250 micrograms/ml) on the in vitro growth of human and murine normal (CFU-GM, IARC 171, FDC-P2) and tumoral (HL60, P388, L1210) hemopoietic cells. A selective cytotoxicity towards tumor cells was observed: an irreversible, concentration dependent inhibition of growth being seen on all tumor cell lines under consideration, while normal cells appeared to be rather insensitive to this drug. In vivo, trichothecolone significantly increased the survival of mice bearing P388 leukemia: a 150 mg/kg/dose, 5 times a day, for 5 days led to a T/C of 145%. Both in vitro and in vivo data suggest that trichothecolone may be an interesting antitumor agent, particularly considering the clear difference in sensitivity of normal and tumor cells to this drug.