Anti-proliferative and Anti-metastatic Potential ofCurcumin Analogue, Pentagamavunon-1 (PGV-1), Toward HighlyMetastatic Breast Cancer Cells in Correlation with ROS Generation

Pentagamavunon-1 (PGV-1) is a curcumin analogue that shows cytotoxic activity invarious cancer cells. In this study, we evaluated the effect of PGV-1 on a highly metastatic breastcancer cell line, the 4T1 cells, as an anti-metastatic and anti-proliferative agent. Cell viability was evaluated using MTT assay; while cell cycle profile, apoptosisincidence, and ROS intracellular level were determined by flow cytometry. Cell senescence wasobserved under senescence-associated-β-galactosidase (SA-β-gal) staining assay. The expressionof matrixmetalloproteinase-9 (MMP-9) was determined using immunoreaction based-ELISA,while other proteins expression were detected using immunoblotting. Curcumin and PGV-1 showed cytotoxic effects on 4T1 cells with IC50 value of 50 and4 μM, respectively. The cytotoxic activity of PGV-1 was correlated to the induction of G2/M cellcycle arrest and cell senescence. Furthermore, PGV-1 increased the accumulation of intracellularROS level. We also revealed that PGV-1 bound to several ROS-metabolizing enzymes,including glyoxalase I (GLO1), peroxiredoxin 1 (PRDX1), N-ribosyldihydronicotinamide:quinone reductase 2 (NQO2), aldo-keto reductase family 1 member c1 (AKR1C1). As an antimetastaticagent, PGV-1 showed less inhibitory effect on cell migration compared to curcumin.However, PGV-1 significantly decreased MMP-9 protein expression in a dose-dependentmanner suggesting it still potent to inhibit metastatic cells. Overall, our findings suggest that PGV-1 is potential to be developed as an antiproliferativeand anti-metastatic agent.