Antiproliferative and Antimetastatic Potential of Curcumin Analogue, Pentagamavunon1 (PGV1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation

Purpose: Pentagamavunon1 (PGV1) is a curcumin analogue that shows cytotoxic activity in various cancer cells. In this study, we evaluated the effect of PGV1 on a highly metastatic breast cancer cell line, the 4T1 cells, as an antimetastatic and antiproliferative agent. Methods: Cell viability was evaluated using MTT assay; while cell cycle profile, apoptosis incidence, and ROS intracellular level were determined by flow cytometry. Cell senescence was observed under senescenceassociatedβgalactosidase (SAβgal) staining assay. The expression of matrixmetalloproteinase9 (MMP9) was determined using immunoreaction basedELISA, while other proteins expression were detected using immunoblotting. Results: Curcumin and PGV1 showed cytotoxic effects on 4T1 cells with IC50 value of 50 and 4 µM, respectively. The cytotoxic activity of PGV1 was correlated to the induction of G2/M cell cycle arrest and cell senescence. Furthermore, PGV1 increased the accumulation of intracellular ROS level. We also revealed that PGV1 bound to several ROSmetabolizing enzymes, including glyoxalase I (GLO1), peroxiredoxin 1 (PRDX1), Nribosyldihydronicotinamide: quinone reductase 2 (NQO2), aldoketo reductase family 1 member c1 (AKR1C1). As an antimetastatic agent, PGV1 showed less inhibitory effect on cell migration compared to curcumin. However, PGV1 significantly decreased MMP9 protein expression in a dosedependent manner suggesting it still potent to inhibit metastatic cells. Conclusion: Overall, our findings suggest that PGV1 is potential to be developed as an antiproliferative and antimetastatic agent.