Quercetin synergistically potentiates the anti-metastatic effect of ۵-fluorouracil on the MDA-MB-۲۳۱ breast cancer cell line

Objective(s): Breast cancer (BC) cells’ ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases ۲ and ۹ (MMP-۲ and MMP-۹) facilitate cancer cell migration. ۵-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 ۵-fluorouracil  on migration of the MDA-MB-۲۳۱ breast cancer cell line. Materials and Methods: The effect of Quercetin, ۵-fluorouracil , and their combination on MDA-MB-۲۳۱ 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-۲ and MMP-۹ was evaluated by quantitative real-time PCR. Results: The IC۵۰ values for Quercetin and ۵-fluorouracil  after ۴۸ hr treatment were ۲۹۵ μM and ۵۲۵ μM, respectively. The combination index (CI) for Quercetin and ۵-fluorouracil  was <۱, indicating synergy between them. The combination of Quercetin plus ۵-fluorouracil  resulted in a significant reduction in migration rate and MMP-۲ and MMP-۹ gene expressions of MDA-MB-۲۳۱ cancer cells compared with the individual application of ۵-FU. Conclusion: Quercetin enhances the suppressory effect of ۵-fluorouracil  on migration of BC cells. The combination of Quercetin and ۵-fluorouracil  can be an attractive field for future studies.

Keywords:

۵-fluorouracil , Anti-metastatic effect , Breast Cancer , Quercetin , Synergism