Fisetin inhibits the proliferation of gastric cancer cells and induces apoptosis through suppression of ERK 1/2 activation

Abstract

The present study aimed to investigate the effect of fisetin on proliferation and apoptosis of gastric cancer cells, as well as the underlying mechanism. Proliferation in SGC7901 cancer and GES-1 normal cells was analyzed using a CCK-8 assay. Apoptosis was analyzed using an Annexin V/Propidium Iodide apoptosis kit and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was analyzed by western blot assay. Treatment of SGC7901 cells with various concentrations (1, 5, 10, 15 and 20 µM) of fisetin for 48 h resulted in a concentration dependent reduction in proliferation. Flow cytometry revealed a marked increase in apoptosis from 5 µM concentration of fisetin after 48 h. The percentage of apoptotic cells increased to 87% following treatment with 15 µM fisetin for 48 h, compared with 2% in control. Treatment of SGC7901 cells with fisetin for 48 h resulted in a reduction in the activation of ERK 1/2 in a concentration-dependent manner. The reduction in activation of ERK 1/2 was significant following treatment with 15 µM fisetin for 48 h. The inhibitory effect of fisetin on activation of ERK 1/2 was further demonstrated using the ERK 1/2 inhibitor, PD98059. The results indicated a significant reduction in the proliferation of SGC7901 cells following treatment with PD98059 (P<0.002). The reduction by PD98059 administration was comparable to that observed following fisetin treatment for 48 h. In conclusion, the current study demonstrates that fisetin inhibits the proliferation of gastric cancer cells and induces apoptosis through suppression of ERK 1/2 activation. Thus, fisetin may have therapeutic applications in the treatment of gastric cancer.

Flavonoids Restore Platinum Drug Sensitivity to Ovarian Carcinoma Cells in a Phospho-ERK1/2-Dependent Fashion

“…Similar to previous reports [ 36 , 37 , 38 , 39 ], the flavonoids fisetin and quercetin were active in stimulating ERK1/2 phosphorylation in OC cells. In contrast, others have claimed that the apoptosis-inducing function of fisetin and quercetin is mediated through ERK1/2-signaling inhibition [ 40 , 41 ], accompanied by ROS generation [ 42 ]. The differences in the outcome of ERK activation are probably due to differences in cellular content.…”

“…There is growing evidence of the anticancer activity of a variety of flavonoids [ 32 , 33 , 34 , 35 ]. Moreover, previous reports have shown flavonoid’s ability to affect the activity of specific signaling pathways, including ERK signaling, through either stimulation [ 36 , 37 , 38 , 39 ] or ERK1/2-signaling inhibition [ 40 , 41 ], accompanied by reactive oxygen species (ROS) generation [ 42 ].…”

Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential

“…In addition, various in vitro and ex vivo studies have also determined the anti-tumor effects of flavonoids mediated through ERK1/2 signaling inhibition. Fisetin is one of the flavonoids that has been found to suppress ERK1/2 signaling in human gastric (SGC7901), hepatic (HepG2), colorectal (Caco-2), and pancreatic cancer cells (Suit-2) [156,157]. In human NCI-H460 NSCLC, fisetin induced ROS generation and suppressed ERK through its phosphorylation [150].…”

MAP Kinases Pathways in Gastric Cancer

“…Indeed, the latter is an important regulator, since its inhibition was associated with a reduced expression of uPA and uPAR. Fisetin is another flavonoid found in fruit and vegetables that has proven to exert an inhibitory effect on the proliferation of SGC7901 cells and induced apoptosis through suppression of ERK1/2 activation [34]. Another recent study has shown how Parameritannin A2, a product extracted from the stems of the plant Urceola huaitingii, has a synergistic effect with doxorubicin in GC cells.…”