期刊
ADVANCED PHARMACEUTICAL BULLETIN
卷 9, 期 3, 页码 445-452出版社
TABRIZ UNIV MEDICAL SCIENCES & HEALTH SERVICES
DOI: 10.15171/apb.2019.053
关键词
Anti-proliferative; Metastatic inhibitor; PGV-1 (curcumin analogue); Reactive oxygen species (ROS); The 4T1 cells
资金
- Indonesian Competence grant, Ministry of Research, Technology and Higher Education, Republic of Indonesia
- World class Professor program, The Ministry of Research, Technology and Higher Education, Republic of Indonesia
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-beta-galactosidase (SA-beta-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 mu M, 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-ribosyldihydronicoiinamide: quinone reductase 2 (NQO2), aldo-lceto reductase family 1 member c1 (AKR1C1). As an anti-metastatic 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 anti-proliferative and anti-metastatic agent.
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