Cleistanthin A causes DNA strand breaks and induces apoptosis in cultured cells

Cleistanthin A is a novel anticancer agent isolated from Cleistanthus colli nus (Rox B). it caused chromatid aberrations in a dose dependent manner. Ho wever, the concentrations that induced the aberrations, neither affected vi ability nor induced DNA strand breaks. Only at higher concentrations and af ter long exposure, DNA strand breaks were observed. Cleistanthin A induced apoptosis in Chinese hamster ovary (CHO) cells, in cervical carcinoma (Si H a) cells and in a p53 deficient cell line K562. Cleistanthin A-induced cell death was low in bcl-2 transfected cells. Cleistanthin A inhibited the inc orporation of [H-3]thymidine into DNA; however, it did not affect the trans port of [H-3]thymidine into these cells. These studies indicate that the cy totoxic effects of cleistanthin A are mediated by the inhibition of DNA syn thesis, induction of DNA damage and apoptosis. (C) 2000 Elsevier Science B. V. All rights reserved.