Anti-proliferation Activity of Salidroside and the Aglycone Tyrosol in Triple-negative Breast Cancer Cells
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Abstract:
The high morbidity and mortality rates that are associated with breast cancer worldwide render the discovery of new drugs critical, and natural products with low toxicity, minimal side effects, multiple targeting, and good efficacy are hot topics in the development of such drugs. Two monomers derived from Rhodiola rosea L., salidroside and tyrosol, have shown good bioactivity. Thus, the ORAC method was used to determine the antioxidant capacity of these compounds, with the triple-negative breast cancer cell line, MDA-MB-231, used as an experimental model to investigate the anti-proliferation effects of the monomers. Cell scratch assay and flow cytometry were performed to detect cell apoptosis and cell cycle stage, and RT-qPCR was employed to further explore related mechanisms. The results showed that salidroside and tyrosol can significantly inhibit the proliferation of MDA-MB-231, with EC50 values of 63.55 and 127.35 μmol/L, respectively. Cell scratch assays showed significantly inhibited cell migration, and after 36 h, salidroside and tyrosol were shown to reduce the cell healing rate from 72.16 % to 27.86 % and 32.69 %, respectively, in the high-concentration groups, while cell cycle and apoptosis assays showed that both salidroside and tyrosol arrest the cell cycle at the G2 phase, promoting apoptosis. RT-qPCR showed that the anti-proliferation effects observed for salidroside are mainly due to up-regulation of the p53 and p21 genes and down-regulation of the Bcl-2, Bcl-xL, and CDK6 genes, whereas the efficacy of tyrosol is associated with up-regulation of the p53, p21, and Bax genes. These results provide theoretical support for further study into the bioactivity of salidroside and tyrosol and provide a theoretical basis for the development of anti-breast cancer drugs in the future.
