Background: Salvia chinensia Benth (SCH) is an herb that has extensively demonstrated antitumor attributes in multiple tumors. However, there are only marginal reports about the impacts of SCH on TNBC-triple negative breast cancer tumorigenesis. Herein, our current research reported the in vitro effects as well as the in vivo antitumor effect, and the fundamental mechanisms of SCH on TNBC.
Methods: In vitro, we measured the antitumor effect of SCH on TNBC through clonogenic assay, cell viability, flow cytometry, apoptosis assay, migration and invasion assay. Meanwhile, breast cancer xenografts with the aid of MDA-MB-231 cells were established to evaluate the therapeutic effect of SCH on TNBC in vivo. To investigate the molecular mechanisms of SCH, bioinformatic analysis, specifically network pharmacology-based analysis, was performed. Then, the comet assay and western blot analyses were applied to confirm the influence of SCH on the DNA damage and repair pathways.
Results: Our results demonstrated that the application of SCH could lead to the reticence of cell proliferation, migration, invasion and the induction of cellular apoptosis caused in TNBC cells. Based on the bioinformatic analysis, we discovered two key compounds of SCH, quercetin and beta-sitosterol, and detected significant synergistic effects of the combined treatment of them on TNBC, especially on the DNA damage of TNBC cells as judged by comet assays. Moreover, substantial inductions of DNA damage were examined after SCH treatment in TNBC cells, as well as quercetin, and beta-sitosterol treatment. Apart from inducing DNA damage, SCH specifically decreased inter-strand crosslink repair pathway and the double-strand breach repair perforated by the homologous recombination pathway. Similar results were also obtained with quercetin and beta-sitosterol treatment.
Conclusion: Taken together, the current investigation elucidates the novel discernment into the therapeutic function of SCH as a DNA damage agent for treatment of TNBC.