lupane and Bone-Neoplasms

Betulin is a lupane type pentacyclic triterpenoid, and commonly found in the bark of birch trees. It displays various pharmacological properties, such as antibacterial, anti-inflammation, antitumor, and antiviral. In this report, we attempted to investigate the anti-proliferative and pro-apoptotic effects of betulin on osteosarcoma cell lines. Our results revealed that betulin significantly decreased cell viability and colony formation in osteosarcoma cell lines. Dose-dependent induction of Annexin V positive cells, activated caspase 8, activated caspase 9, activated caspase 3, and the cleavage of poly (ADP-ribose) polymerase were observed after the treatment with betulin, indicating betulin induces apoptosis in osteosarcoma cell lines. mTOR has been identified as a key modulator of autophagy in response to different stresses. In this study, we found that the treatment with betulin suppressed the activation of mTOR, and increased the level of LC 3-II, the autophagy marker, in osteosarcoma cell lines. Co-administration of the autophagy inhibitor chloroquine significantly rescued the cell viability and the clonogenic activity in betulin-treated osteosarcoma cell lines. Our data showed that betulin induced autophagy, and the up-regulated autophagy positively contributed to the apoptosis. Taken together, our findings suggested that betulin may serve as a promising anti-proliferative agent for treating osteosarcoma.

Topics: Apoptosis; Autophagy; Bone Neoplasms; Caspase 3; Caspases; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Osteosarcoma; TOR Serine-Threonine Kinases; Triterpenes