Deoxypodophyllotoxin induces cell cycle arrest and apoptosis in human cholangiocarcinoma cells.

Deoxypodophyllotoxin (DPT), a naturally occurring flavolignan, has a broad range of biological effects, including anti-inflammatory, anti-viral and anticancer properties. The present study investigated the anti-proliferative effect of DPT on human cholangiocarcinoma QBC939 and RBE cell lines and its underlying mechanisms of inducing cytotoxicity. MTT assays demonstrated that DPT inhibited the viability of the QBC939 and RBE cells in a dose and time-dependent manner. In addition, DPT treatment resulted in G2/M phase cell cycle arrest associated with the downregulation of Cyclin B and cyclin dependent kinase 1 and caused an increase in apoptosis that was confirmed by characteristic morphological changes. Apoptosis was accompanied by increasing B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein ratios and activated expression of caspase-3, -8 and -9. These findings suggested that DPT may be a novel anticancer agent against human cholangiocarcinoma.