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Abstract

Among various subtypes of breast cancer, triple-negative breast cancer (TNBC) is aggressive breast cancer. Doxorubicin is the standard therapy used for treating TNBC, but poses a risk of severe adverse effects affecting patient compliance. Hence, there is a need for therapy that reduces the adverse effect and increase compliance for better overall pathological complete response (pCR). Metformin, widely used as an antidiabetic, has gained momentum for its preventive potential and delaying various cancers, including breast cancer, owing to its high safety and better tolerability. Hesperidin, commonly found in citrus fruits, is an integral part of daily diet and consumed worldwide. The objective of the current study was to investigate the potentiation of anti-proliferative effect of doxorubicin using metformin and hesperidinon MDA-MB-468 human breast cancer cell line. The IC50 concentration of doxorubicin (1 µM) was combined with nontoxic doses of metformin (0.5, 1, and 2 mM) and hesperidin (5, 10, and 20 µM). Metformin (1 mM) and hesperidin (5 µM) in combination with doxorubicin (1 µM) inhibited the migration of MDA-MB-468 cells in a scratch assay. In Annexin V-FITC assay, a combination of doxorubicin, metformin, and hesperidin exhibited an increase in cells in late and early apoptosis phase.Further, when cell cycle analysis was performed, cells shifted from G0/G1 phase to S phase, ultimately leading to the arrest of cells in S phase. Hence, the results are conclusive of potentiation of the antiproliferative effect of doxorubicin using metformin and hesperidin on human breast cancer cell line MDA-MB-468. INTRODUCTION:Breast cancer (BC) is the leading cause of cancer, accounting for 2.3 million cases worldwide 1 . Triple-negative breast cancer (TNBC) is the most aggressive cancer among various breast cancer subtypes. TNBC accounts for 10-20 % of cases of BC 2 .