Synergistic Role of Thymoquinone on Anticancer Activity of 5-Fluorouracil in Triple Negative Breast Cancer Cells

Abstract

Background: Triple Negative Breast Cancer (TNBC) is considered as the most deadly subtype of breast cancer, because of heterogeneity, less treatment options and resistance to chemotherapy.

Objective: To find out an efficient chemotherapeutic options, in this study we have investigated the combined therapy of 5-Fluorouracil (5-FU) and thymoquinone (TQ) against TNBC cell lines BT-549 and MDA-MB-231.

Methods: We have 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 cell cycle and apoptosis.

Results: Experimental results suggest that both of 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 to be more effective in controlling cell growth, while TQ was found to be more effective in inducing apoptosis, but in both cases, their combination was most effective. TQ was found more effective in increasing and BAX/BCL-2 ratio, while 5-FU was more effective in inhibiting thymidylate synthase. They showed significant increasing effects on caspases and P53 and decreasing effect on CDK-2, where their combination was found most effective.

Conclusion: Thus, TQ and 5-FU probably showed 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 good choice in drug development for TNBC treatment.

Keywords: 5-fluorouracil; Triple negative breast cancer; apoptosis; cell cycle; combination therapy; thymoquinone.