Anticancer potential of cleistanthin A isolated from the tropical plant Cleistanthus collinus

A diphyllin glycoside called cleistanthin A was isolated from the tropical plant Cleistanthus collinus and its anticancer potential was assessed. This compound showed preferential cytotoxicity in several tumor cell lines. The GI(50) values for normal cell lines were between 10(-6) and 10(-7) M while for tumor cells the values ranged from 10(-7) to 10(-9) M. When the cytoto xicity of this compound was compared with five anticancer drugs, cleistanth in A was found to be most effective for the oral carcinoma cell line KB and the cervical carcinoma cell line SiHa. The efficacy of cleistanthin A in a rresting tumor growth was assessed in mice harboring Dalton's ascites lymph oma and a solid tumor S-180 sarcoma. In both cases, the tumor volume was dr astically reduced upon treatment with cleistanthin A. This compound also in creased the life span of mice with S-180 sarcoma to a similar extent as tha t done by cisplatin (CDDP: cis-diamminedichloroplatinum) and etoposide. How ever, cleistanthin A was less toxic than these drugs because it did not aff ect the body weighs and lymphocyte count in treated animals. Although the m olecular mechanisms of action of cleistanthin A in arresting cell growth ar e yet to he explored in various perspectives, our present results indicate that this compound arrests growth by inhibiting DNA synthesis and cell divi sion and by driving cells to apoptosis. Time-lapse video microscopic record ings of cleistanthin A-treated cells showed vigorous membrane blebbing, cha racteristic of apoptosis.