Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation
Penulis/Author
Prof. Dr. apt. Edy Meiyanto, M.Si. (1); Herwandhani Putri (2); Yonika Arum Larasati (3); Dr. Sci. apt. Rohmad Yudi Utomo, M.Sc. (4); Dr. Riris Istighfari Jenie, M.Si., Apt. (5); Dr. apt. Muthi' Ikawati, M.Sc. (6); BENI LESTARI (7); Noriko Yoneda-Kato (8); Ikuko Nakamae (9); Masashi Kawaichi (10); Jun-ya Kato (11)
Tanggal/Date
2019
Kata Kunci/Keyword
Abstrak/Abstract
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-?-galactosidase (SA-?-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 ?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-ribosyldihydronicotinamide: quinone reductase 2 (NQO2), aldo-keto 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.
Rumpun Ilmu
Analisis Farmasi dan Kimia Medisinal
Bahasa Asli/Original Language
English
Level
Internasional
Status
Dokumen Karya
No
Judul
Tipe Dokumen
Aksi
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apb-9-445.pdf
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