Synergistic Role of Thymoquinone on Anticancer Activity of 5-fluorouracil in Triple-Negative Breast Cancer Cells.
Anticancer Agents Med Chem. 2021 Jun 24. Epub 2021 Jun 24. PMID: 34170813
BACKGROUND: Triple-negative breast cancer (TNBC) is considered the most deadly subtype of breast cancer because of heterogeneity, fewer treatment options, and resistance to chemotherapy.
OBJECTIVE: We investigated the combined therapy of 5-Fluorouracil (5-FU) and thymoquinone (TQ) against TNBC cell lines BT-549 and MDA-MB-231 in this study to find out efficient chemotherapeutic options.
METHODS: We tested 5-FU and TQ alone and in combination (5-FU + TQ) to observe the cellular growth, cell cycle, and apoptosis status of BT-549 and MDA-MB-231 cells. Also, we have measured the mRNA level expression of genes related to the cell cycle and apoptosis.
RESULTS: Experimental results suggest that both 5-FU and TQ are effective in controlling cell growth, cell cycle, and inducing apoptosis, but their combination is much more effective. 5-FU was found more effective in controlling cell growth, while TQ was found more effective in inducing apoptosis, but in both cases, their combination was most effective. TQ was found to be more effective in increasing and BAX/BCL-2 ratio), while 5-FU was more effective in inhibiting thymidylate synthase. They had shown significant increasing effects on caspases and P53 and decreasing effects on CDK-2, where their combination was found most effective.
CONCLUSIONS: Thus, TQ and 5-FU probably showed a synergistic effect on both of cell cycle and apoptosis of tested TNBC cell lines. Our study reveals that TQ can synergise 5-FU action and increase its anticancer efficiency against TNBC cells, which might be a good choice in drug development for TNBC treatment.