Swertiamarin exerts anticancer effects on human cervical cancer cells via induction of apoptosis, inhibition of cell migration and targeting of MEK-ERK pathway

摘要

Purpose: To investigate the anticancer effects of swertiamarin against taxol-resistant human cervical cancer cells. Methods: Cell viability was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5–diphenyl tetrazolium bromide (MTT) assay while colony survival was evaluated by clonogenic assay. Apoptotic cell death was assessed by AO/ETBR staining and western blotting techniques. The levels of reactive oxygen species (ROS) were measured using 2,7, dicholoro dihydrofluoresceindiacetate (H2DCFDA) staining. Cell migration and invasion were monitored with Transwell chamber assay. Western blotting assay was used to determine the ex pression levels of proteins of the MEK/ERK signaling pathway. Results: Swertiamarin induced dose- and time-dependent inhibition of proliferation of HeLa cervical cancer cells (p 0.05). It also suppressed the colony formation potential of HeLa cells, and induced various structural modifications in HeLa cells. Swertiamarin exposure resulted in the formation of early-apoptotic, late-apoptotic and necrotic cells, and significant modulation of apoptosis-allied proteins. It was observed that the migration and invasion of HeLa cells were potentially suppressed in dose-reliant fashion by swertiamarin. Western blotting results showed that the ex pressions of p-MEK and p-ERK were markedly reduced, while those of MEK and ERK were unaffected (p 0.05). Conclusion: Swertiamarin exerts in vitro anticancer activity against cervical cancer cells (HeLa). Thus, it is promising for use in cervical cancer chemotherapy. However, there is need for confirmation of these findings through further in vivo and in vitro investigations.