Hesperidin Enhanced the Antimigratory Activity and Senescence-Mediated G2/M Arrest Effect of PGV-1 Against T47D Luminal Breast Cancer Cells

Luminal breast cancer cells exhibit proliferative and metastatic characteristics. This study aims to confirm the effect of the combination treatment of Pentagamavunone-1 (PGV-1), a potent anticancer candidate, and hesperidin on the luminal breast cancer cell line T47D covering the evaluation of cytotoxic and antimigratory activities of PGV-1 and analyzing the most probable protein targets of PGV-1 and hesperidin. Cytotoxic effects were assayed via trypan blue exclusion. Cell cycle profiles were analyzed through flow cytometry. Cellular senescence phenomena were observed through senescence-associated β-galactosidase assay. Cell migration was evaluated by performing a scratch wound healing assay. Molecular target prediction was conducted through bioinformatics analysis with UALCAN and molecular docking with Molecular Operating Environment (MOE) software. PGV-1 showed considerably stronger cytotoxicity (IC50 value of 2 μM) than hesperidin (IC50 value of 200 μM). However, the combination of PGV-1 and hesperidin exhibited a synergistic effect (combination index < 0.3) and increased the populations of cells at the G2/M phase and senescent cells. This effect might be correlated to its antiproliferative properties. In addition, the scratch wound healing assay showed that the combination treatment inhibited cell migration remarkably. Molecular docking demonstrated the potential interactions of PGV-1 and hesperidin with their protein targets, i.e., KIF1, CDK1, TOP2A, CA12, ESR1, FN1, and TYMS, in the cell cycle machinery. Altogether, the findings of this work strengthen the evidence showing that combining PGV-1 with hesperidin enhances the anticancer properties of PGV-1 against luminal breast cancer. Copyright © 2024 by Indonesian Journal of Pharmacy (IJP).