Cryptotanshinone has diverse effects on cell cycle events in melanoma cell lines with different metastatic capacity
mesheuropmc: nervous system diseases
Background and Purpose: Cryptotanshinone (CTs) is a major active component of Salvia miltiorrhiza, which is often used as Chinese herbal medicine in cancer therapy. Here, we systematically assessed the anti-tumor effect of CTs on two melanoma cell lines with low/high metastatic capacity (B16/B16BL6). Experimental Approach: MTT and LDH assays were used to evaluate cell growth and cytotoxicity. We assessed the effect of CTs on cell apoptosis or proliferation by Annexin V, TUNEL or BrdU assay. Cell cycle distribution was detected by flow cytometry. The integrity of cell cycle checkpoints was determined by mutational analyses of B-RAF and N-RAS, and the expression of cell cycle associated proteins by western blotting. Key Results: Treatment with CTs had no obvious effect on cell apoptosis, but significantly inhibited cell proliferation. CTs induced the expression of p53, Chk1 and Chk2 in both B16 and B16BL6. Interestingly, CTs induced G1 arrest in B16BL6 cells, together with an increase in protein levels of p21. By contrast, in B16 cells, CTs induced the G2/M arrest through induction of Cdc25c. Regulation of Cyclin A1, Cyclin B1 and Cdk1/cdc2 expression level might contribute to the different cell cycle patterns in B16 and B16BL6 after CTs treatment. 2 Conclusions and Implications: CTs could have opposite effects on cell cycle events in melanoma cell lines with different metastatic capacity. This property might offer an opportunity to study the mechanisms underlying the different anti-tumor effects of CTs on B16 and B16BL6.
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