Comparative effects of selected plant polyphenols, gallic acid and epigallocatechin gallate, on matrix metalloproteinases activity in multidrug resistant MCF7/DOX breast cancer cells

Abstract

The aim of the study was to investigate the effect of selected polyphenols: gallic acid (GA) and epigallocatechin gallate (EGCG) on matrix metalloproteinase (MMP-2 and MMP-9) activity in multidrug resistant (MDR) human breast adenocarcinoma cells: MCF7/DOX cells and obtained recently in our laboratory MCF7/DOX500 cells by the permanent selection of MCF7/DOX cells with 500 nM doxorubicin (DOX). The activity of MMP-2 and MMP-9 and the effect of studied polyphenols on these matrix proteases were examined by gelatin zymography assays. We have found that the activity of MMP-2 and MMP-9 significantly increased in resistant MCF7/DOX and MCF7/DOX500 cells whereas they were not detected in sensitive MCF7 cells. It was also observed that GA (30, 60, 100 and 120 µM) and EGCG (5, 10 and 20 µM) caused a comparable concentration-dependent inhibition of MMP-2 and MMP-9 activity in MCF7/DOX and MCF7/DOX500 cells. Control experiments confirmed that examined compounds in these ranges of concentration did not affect the cell growth of MCF7/DOX and MCF7/DOX500 sublines (80-100% of control cell growth was observed in the presence of studied polyphenols).

Treponema denticolaincreases MMP-2 expression and activation in the periodontium via reversible DNA and histone modifications

“…It was also investigated in many clinical trials for treatment of several disorders, including hematological and neoplastic disorders (Liu et al , 2005, Mirza et al , 2010, Chen et al , 2012). Regarding the effect of EGCG on MMP-2 expression in our study, the data are inconsistent with other studies, which reported the ability of EGCG to inhibit MMP-2 in different cancer cells (Chang et al , 2014a, Nowakowska et al , 2016). This inconsistency may be due to the use of different cell types, different concentrations of EGCG, or both.…”

Epigallocatechin‐3‐gallate enhances differentiation of acute promyelocytic leukemia cells via inhibition of PML‐RARα and HDAC1

“…Here, we have shown that EGCG at 100 μM concentration is able to decrease the expression of ABCB1 and ABCC1 in HL60 and NB4 cells, whereas ATRA failed to show such an effect. This effect is in agreement with previous findings that showed EGCG reduced MDR at various cancer cells (Lyn‐Cook et al, ; Mei, Wei, & Liu, ; Nowakowska & Tarasiuk, ; Qian, Wei, Zhang, & Yang, ; Wen et al, ) and supports the notion that EGCG may suppress drug resistance via downregulation of ABC transporters.…”

Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer

“…The synergistic effect occurs due to inhibition of P-gp expression by EGCG, thus increasing the incorporation of curcumin in breast cancer cells, leading to enhancement of apoptosis and regulation of apoptosis proteins [238]. A similar effect was observed for the association between EGCG and gallic acid in multidrug resistant MCF7/DOX breast cancer cells [220]. The inhibitory effect of EGCG upon P-gp increases gallic acid concentration in cancer cells leading to inhibition of matrix metaloproteinases (MMP-2, MMP-9).…”

“…In addition, association between gallic acid and ECGC attenuated MDR in doxorubicin-resistant breast cancer cells through a concentration-dependent inhibition of metalloproteinases (MMP-2 and MMP-9). It is well known that metalloproteinases are involved in the degradation of extracellular matrix by metastatic cancer cells [220]. Another mechanism involved in gallic acid overcoming MDR is the inhibition of Src/STAT3-mediated signaling and the decrease in the expression of STAT3-regulated tumor-promoting genes, therefore inducing apoptosis and cell cycle arrest.…”