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

Abstract

Cleistanthin A is a novel anticancer agent isolated from Cleistanthus collinus (Rox B). It caused chromatid aberrations in a dose dependent manner. However, the concentrations that induced the aberrations, neither affected viability nor induced DNA strand breaks. Only at higher concentrations and after long exposure, DNA strand breaks were observed. Cleistanthin A induced apoptosis in Chinese hamster ovary (CHO) cells, in cervical carcinoma (Si Ha) 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 incorporation of [³H]thymidine into DNA; however, it did not affect the transport of [³H]thymidine into these cells. These studies indicate that the cytotoxic effects of cleistanthin A are mediated by the inhibition of DNA synthesis, induction of DNA damage and apoptosis.