CELL-CYCLE PHASE-SPECIFIC CYTOTOXICITY OF THE ANTI-TUMOR AGENT MAYTANSINE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (8) , 3152-3155
Abstract
The effects of maytansine on the cell cycle kinetics of HeLa [human cervical carcinoma] cells were studied. Maytansine is a very potent mitotic inhibitor and it has no effect on marcomolecular synthesis. Maytansine-induced cytotoxicity was dependent on the position of the cell in the cell cycle. Mitotic and G2 cells were most sensitive to this agent, while G1 phase cells were the most resistant, with S-phase cells being intermediate. Small (0.82 .times. 10-8 M) fractionated doses given at an interval of 8 h were more cytotoxic than was a large (1.64 .times. 10-8 M) single dose. In evaluating the drug combinations, the schedule in which 1-.beta.-D-arabinofuranosylcytosine treatment was followed by maytansine treatment exhibited greater cell kill than the reverse sequence. No schedule-dependent effects were observed when maytansine was tried in combination with adriamycin.