GROWTH-INHIBITION OF K-RAS-EXPRESSING TUMORS BY A NEW VINCA ALKALOID,CONOPHYLLINE, IN NUDE-MICE

Conophylline, a new vinca alkaloid isolated from the plant Ervatamia m icrophylla induced normal flat morphology in K-ras-NRK and K-ras-NIH c ell lines, and lowered the increased uptake of 2-deoxyglucose in K-ras -NRK cells. Conophylline inhibited the growth of K-ras-NRK cells, but this inhibition was reversible. The alkaloid also inhibited the growth of K-ras-NRK and K-ras-NIH3T3 tumours transplanted into nude mice. On the other hand, it showed no effect on survival of the mice loaded wi th L1210 leukaemia. Thus, conophylline is a new antitumour vinca alkal oid that induced normal phenotypes in ras-expressing cells.