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 GI50 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 cytotoxicity of this compound was compared with five anticancer drugs,
cleistanthin 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 arresting
tumor growth was assessed in mice harboring Dalton's
ascites lymphoma and a solid
tumor S-180
sarcoma. In both cases, the
tumor volume was drastically reduced upon treatment with
cleistanthin A. This compound also increased the life span of mice with S-180
sarcoma to a similar extent as that done by
cisplatin (CDDP:
cis-diamminedichloroplatinum) and
etoposide. However,
cleistanthin A was less toxic than these drugs because it did not affect the
body weight and lymphocyte count in treated animals. Although the molecular mechanisms of action of
cleistanthin A in arresting cell growth are yet to be explored in various perspectives, our present results indicate that this compound arrests growth by inhibiting
DNA synthesis and cell division and by driving cells to apoptosis. Time-lapse video microscopic recordings of
cleistanthin A-treated cells showed vigorous membrane blebbing, characteristic of apoptosis.