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. Exploration of the effective treatment with minimum side effects is necessary. This study aimed to confirm the combination treatment of a potent anticancer candidate PGV-1 and hesperidin on luminal breast cancer cells, T47D, covering its cytotoxic and anti-migratory activities. PGV-1 showed much stronger cytotoxicity with an IC50 value of 2 μM than that of hesperidin (200 μM) as evaluated by trypan blue exclusion assay, but the combination of the two compounds exhibited a synergistic effect. Propidium iodide (PI) staining with flow cytometry proved that the combination treatment increased the cell population in the G2/M phase. Additionally, the combination treatment increased senescent cells as shown in senescence associated β-galactosidase (SA-β-gal) assay which might correlate to its antiproliferative properties. In addition, the scratch wound healing assay showed that the combination also inhibited cell migration significantly. Molecular docking of the two compounds demonstrated potential interaction with their protein targets in cell cycle machinery, i.e. KIF1, CDK1, TOP2A, CA12, ESR1, FN1, and TYMS. Altogether, these findings strengthen the evidence of anti-cancer properties enhancement of PGV-1 in luminal breast cancer through combining the compound with hesperidin.