Quercetin synergistically potentiates the anti-metastatic effect of 5-fluorouracil on the MDA-MB-231 breast cancer cell line

Abstract

Objective(s): Breast cancer (BC) cells’ ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) facilitate cancer cell migration. 5-fluorouracil is a frequently applied chemotherapeutic agent in cancer treatment with destructive side effects on normal tissues. Hence, researchers have focused on finding a way to reduce the dose of chemotherapeutic drugs. Quercetin, a natural polyphenolic compound, has inhibitory effects on proliferation and migration of tumor cells. This study evaluated the effect of the combination of Quercetin and 5-fluorouracil on migration of the MDA-MB-231 breast cancer cell line. Materials and Methods: The effect of Quercetin, 5-fluorouracil , and their combination on MDA-MB-231 breast cancer cell proliferation was investigated through MTT assay. Inhibition of tumor cell migration was examined by wound healing assay. Finally, the effect of treatments on gene expression of MMP-2 and MMP-9 was evaluated by quantitative real-time PCR. Results: The IC50 values for Quercetin and 5-fluorouracil after 48 hr treatment were 295 μM and 525 μM, respectively. The combination index (CI) for Quercetin and 5-fluorouracil was <1, indicating synergy between them. The combination of Quercetin plus 5-fluorouracil resulted in a significant reduction in migration rate and MMP-2 and MMP-9 gene expressions of MDA-MB-231 cancer cells compared with the individual application of 5-FU. Conclusion: Quercetin enhances the suppressory effect of 5-fluorouracil on migration of BC cells. The combination of Quercetin and 5-fluorouracil can be an attractive field for future studies.

Keywords

• 5-fluorouracil
• anti-metastatic effect
• breast cancer
• quercetin
• synergism