Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 9 3 2019 08 01 Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation 445 452 10.15171/apb.2019.053 EN Edy Meiyanto https://orcid.org/http://orcid.org/0000-0002-0886-6322 Herwandhani Putri Yonika Arum Larasati https://orcid.org/0000-0002-9423-0768 Rohmad Yudi Utomo https://orcid.org/0000-0003-4803-9417 Riris Istighfari Jenie https://orcid.org/0000-0002-0230-6260 Muthi Ikawati https://orcid.org/0000-0002-5968-0130 Beni Lestari https://orcid.org/0000-0002-5658-0572 Noriko Yoneda-Kato Ikuko Nakamae Masashi Kawaichi Jun-Ya Kato Journal Article 10.15171/apb.2019.053 2018 10 04 2019 04 14 Purpose: Pentagamavunon-1 (PGV-1) is a curcumin analogue that shows cytotoxic activity in various cancer cells. In this study, we evaluated the effect of PGV-1 on a highly metastatic breast cancer cell line, the 4T1 cells, as an anti-metastatic and anti-proliferative 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 senescence-associated-β-galactosidase (SA-β-gal) staining assay. The expression of matrixmetalloproteinase-9 (MMP-9) was determined using immunoreaction based-ELISA, while other proteins expression were detected using immunoblotting. Results: Curcumin and PGV-1 showed cytotoxic effects on 4T1 cells with IC50 value of 50 and 4 µM, respectively. The cytotoxic activity of PGV-1 was correlated to the induction of G2/M cell cycle arrest and cell senescence. Furthermore, PGV-1 increased the accumulation of intracellular ROS 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 antimetastatic agent, PGV-1 showed less inhibitory effect on cell migration compared to curcumin. However, PGV-1 significantly decreased MMP-9 protein expression in a dose-dependent manner suggesting it still potent to inhibit metastatic cells. Conclusion: Overall, our findings suggest that PGV-1 is potential to be developed as an antiproliferative and anti-metastatic agent.