Combination Treatment of Docetaxel with Phytol or Thymol Additively Inhibits the Proliferation of Breast Cancer Cells and Downregulates the Expression of Cancer Stem Cell Markers
摘要
Breast cancer stem cells are responsible for breast cancer tumorigenesis, metastasis, drug resistance, and relapse. Targeting breast cancer stem cells with phytochemicals plays a crucial role in breast cancer treatment. This study aimed to investigate the inhibitory effects of docetaxel and its combination with phytol or thymol on the proliferation of breast cancer MCF-7 cells and the downregulation of cancer stem cell markers. According to the MTT assay, docetaxel, phytol, and thymol exhibited cytotoxic effects with IC50 values of 20.88, 39, and 642 µM, respectively. However, when combined with phytol or thymol, the IC50 of docetaxel decreased to 11.3 and 12.1 µM, indicating enhanced cytotoxicity. The combination of docetaxel with either thymol or phytol at their respective IC50 concentrations produced an additive anticancer effect, as demonstrated by the combination index calculation and isobologram analysis using CompuSyn software. According to real-time PCR analysis, the combined treatment of MCF-7 cells with docetaxel and either thymol or phytol was more effective in downregulating CD133, CD44, and ABCB1 than docetaxel alone. Moreover, the expressions of OCT4 and SOX2 reduced significantly following co-treatment with docetaxel and thymol. In conclusion, combining docetaxel with either phytol or thymol enhances its cytotoxic effects against MCF-7 cancer cells. Furthermore, the combination treatment was more effective than docetaxel alone in reducing the cancer stem cell marker, suggesting it may improve chemosensitivity to docetaxel and help prevent cancer recurrence in patients. In summary, the goal of using multi-drug combinations—including chemotherapy agents and phytochemical compounds—is to maximize cytotoxicity against cancer cell lines while reducing adverse side effects.
Graphical Abstract