Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation

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-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.

Curcumin Analogs Induce Apoptosis and G2/M Arrest In 4T1 Murine Triple-Negative Breast Cancer Cells

“…Furthermore, curcumin analog of A501 and WZ35 induces G2/M cell cycle arrest in non-small lung cancer cells, and prostate cancer cells (Xia et al, 2014;Zhang et al, 2015) and EF24 also induce G2/M arrest in MAD-MB cell line by increasing level of ROS, while simultaneously decrease the cellular level of GSH (Adams et al 2005b). Results of this present study was supported by a previous study that demonstrated G2/M cell cycle arrest upon PGV-1 treatment ( 2 and 4 μM) in 4T1 cells (Meiyanto et al 2019). Moreover, the same author showed S phase arrest upon curcumin treatment in concentration of 25 μM in 4T1 cells.…”

Resveratrol, Curcumin and Piperine Alter Human Glyoxalase 1 in MCF-7 Breast Cancer Cells

“…Santel and colleagues [ 45 ] found that specific GLO1 activity in curcumin-treated JIMT-1 breast carcinoma cells was lower than in non-treated cells, decreasing dose-dependently. In addition, Meiyanto et al [ 46 ] reported that curcumin finely binds to GLO1 and induces autophagy in 4T1 cells.…”

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

“…In addition to this, several curcumin nanoformulations have been prepared to provide shielding to curcumin from hydrolysis and to increase its retention period in the body [ 93 ]. There exist few curcumin-based nanoformulations with more significant pharmaceutical potential in diagnosing various human diseases [ 94 ], a number of studies have shed light on their anti-proliferative potential [ 95 , 96 ], but only a scarce amount of them have searched for the therapeutic effects of curcumin nanoformulations in PC [ 97 ]. So, here, we have summarized the curcumin nanoformulations and their significance in regulating PC cell growth.…”