Effects and mechanism of bakuchiol-induced S-phase cell cycle arrest in human breast cancer MCF-7 cells / 中草药

ABSTRACT

Objective: To investigate the cell growth inhibitory effect and molecular mechanism of bakuchiol against human breast cancer MCF-7 cells. Methods: The growth inhibitory effect of bakuchiol on MCF-7 cells was tested by MTT assay. Flow cytometry was used to investigate the distribution of cell cycle and ROS generation. Fluorescence microscope was used to observe the change of cell nucleus. Western blotting was used to detect the expression of the protein related to cell cycle and MAPK family. The ROS scavenger and inhibitors of MAPK family were introduced to investigate the effect on the growth inhibitory rate and the levels of cell cycle related protein by bakuchiol. Results: Bakuchiol inhibited the cell growth on the MCF-7 cells in dose- and time-dependent manner, which showed stronger effect than that of 5-fluorouracil. Furthermore, bakuchiol induced S-phase arrest in MCF-7 cells via ROS generation. The production of ROS up-regulated p-p53 and p21 expression, and then decreased CDK2 and CyclinA2. The changes of bakuchiol on these proteins could be reversed by the ROS scavenger Trion, indicating that ROS was associated with bakuchiol-induced S-phase arrest. In addition, pretreatment with p38MAPK inhibitor SB203580 decreased bakuchiol-caused ROS generation, suggesting that the production of ROS was dependent on p38MAPK pathway. Conclusion: The proliferation inhibitory effect of bakuchiol on MCF-7 cells is related with S-phase cell cycle arrest, and ROS plays a role in the bakuchiol-induced S-phase arrest.