Quercetin Suppresses Intracellular ROS Formation, MMP Activation, and Cell Motility in Human Fibrosarcoma Cells

Abstract

Cell metastasis is a major cause of death from cancer and can arise from excessive levels of oxidative stress. The objective of this study was to investigate whether the natural flavonoid quercetin can inhibit matrix metalloproteinase (MMP)-2 and -9 activities through the attenuation of reactive oxygen species (ROS) formation, an event expected to lead to the inhibition of cell motility. To induce sustained ROS formation, cells were treated with phenazine methosulfate (PMS; 1 μM). Noncytotoxic concentrations of quercetin inhibited PMS-induced increases in cell motility in HT1080 human fibrosarcoma (HT1080) cells. While nearly 100% of cells were observed to migrate after 24 h of PMS treatment, quercetin significantly (P < 0.01) suppressed this effect. We also found that quercetin, up to 10 μg/mL, attenuated PMS-induced MMP-2 activation. We then investigated whether the decreased levels of MMP-2 activation could be attributable to lower levels of ROS formation by quercetin. We found that quercetin treatments significantly attenuated PMS-induced ROS formation (P < 0.01) and resulted in decreased cell motility associated with a reduction in MMP-2 and -9 activitiy in HT1080 cells, even in the absence of PMS treatment. Collectively, these results suggest that quercetin inhibits cell motility via the inhibition of MMP activation in HT1080 cells in the presence and absence of PMS. This is likely to be a result of the suppression of intracellular ROS formation by quercetin.

Galangin and Kaempferol Suppress Phorbol-12-Myristate-13-Acetate-Induced Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma HT-1080 Cells

“…Although suppression of MMP-9 expression by kaempferol, quercetin, and morin was reported in different conditions Lee et al, 2013;Lin et al, 2010;Sivaramakrishnan and Niranjali Devaraj, 2009;Yi et al, 2012), our study showed that MMP-9 secretion from HT-1080 cells was severely decreased by galangin as well as kaempferol, and moderately decreased by fisetin. Interestingly, quercetin weakly affected and morin did not affect MMP-9 secretion.…”

Oxidation events and skin aging

“…These events may be triggered by ROS and can be reduced by antioxidants, such as quercetin (Lee et al, 2013). Moreover, gradual oxidative damage during life to DNA bases in genes coding for the dermal matrix components collagen and elastin leads to their reduced expression in aged skin (Uitto, 1979).…”

Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

“…More specifically, studies have shown that quercetin has the capacity to decrease MMP-2 and -9 expression that have a proeminent effect on cancer cell invasion and metastization [3,[58][59][60][61][62][63][64]. In this context, in 2004 Zhang and colleagues [60] had demonstrated that quercetin is capable of reducing the invasive potential of a melanoma cell line by decreasing pro-MMP-9 through PKC pathway [60].…”