Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production

Abstract

Galangin, a flavonoid isolated from the rhizome of Alpinia officinarum (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. It suppressed cell proliferation accompanied by reduced Ki67 and PCNA expression, promoted apoptosis shown by decreased Bcl-2 and elevated cleaved caspase-3 and cleaved PARP. And, galangin significantly inactivated JAK2/STAT3 pathway. When STAT3 was overexpressed, the proliferation inhibition and apoptosis promotion induced by galangin were abrogated. Meanwhile, galangin increased ROS accumulation, and reduced Nrf2 and NQO-1, but elevated HO-1 in MGC 803 cells. NAC, a ROS scavenger, rescued ROS over-accumulation and proliferation inhibition of galangin. STAT3 overexpression also counteracted excessive ROS accumulation induced by galangin. Consistent with the in vitro experiments, in nude mice exnografted with MGC 803 cells, galangin inhibited tumor growth and reversed the abnormally expressed proteins, such as p-JAK2, p-STAT3, Bcl-2, cleaved caspase-3, cleaved PARP, and Ki67. Taken together, galangin was suggested to inhibit the growth of MGC 803 cells through inducing apoptosis and decreasing cell proliferation, which might be mediated by modulating STAT3/ROS axis. Our findings implicate a potential application of galangin for gastric cancer therapy possibly with low toxicity.

Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer

“…On the other hand, one of the biggest challenges in cancer treatment is the ongoing autocrine and paracrine activation of proinflammatory transcription factors, such as NF- κB, signal transducer and activator of transcription 3 (STAT-3), activator protein 1 (AP-1), forkhead box protein M1 (FOXM1), and hypoxia-inducible factor 1α (HIF-1α) that drive the overproduction of diverse mediators of inflammation—inflammatory cytokines, chemokines, cellular adhesion molecules, anti-apoptotic molecules, and iNOS [ 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 ]. Regarding propolis and its components, numerous studies have demonstrated the anti-inflammatory effects of various flavonoids [ 1 , 2 , 3 , 4 , 38 , 174 , 198 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 ]. The anti-inflammatory properties of several flavonols (quercetin, rutin, and morin) and flavanones (hesperetin and hesperidin) were examined in animal models of acute and chronic inflammation.…”

“…The observed anti-inflammatory effects of propolis are attributed to the presence of flavonoids, especially galangin. Galangin inhibits COX and LOX activity, and reduces PGE2 release and the expression of the inducible isoform of COX (COX-2) [ 161 , 249 , 250 ]. Besides galangin, many authors [ 240 , 251 , 252 , 253 , 254 ] have emphasized the anti-inflammatory contribution of quercetin.…”

Antioxidant properties of bee propolis and an important component, galangin, described by X-ray crystal structure, DFT-D and hydrodynamic voltammetry

“…In a recent study, galangin and chrysin were determined to be the most abundant polyphenols of a brown propolis extract [ 3 ]. Galangin, 3,5,7-trihydroxyflavone, is recognized to have significant beneficial biological activities such as anticancer [ 4 , 5 ], antioxidant [ 6 , 7 ]. Galangin is also found in plants such as Alpinia officinarum Hance (Zingiberaceae), or lesser galangal, and has been used as a spice and in herbal remedies for a variety of ailments in Ayurvedic and Chinese medicine for centuries [ 8 , 9 ].…”

Regulation of microglia related neuroinflammation contributes to the protective effect of Gelsevirine on ischemic stroke

“…The activities of NOX family members (including NOX1-5, DUOX1, and DUOX2) are tightly related to the generation of ROS ( 48 ). STAT3 is also reported to bind to the NOX1 promoter and increase the production of NOX1 which subsequently stimulates the production of O2 •− ( 49 ). Therefore, the regulation of overactivated STAT3 in microglia is essential to regulate microglial activation, ROS level and neuroinflammation, all of which are tightly related to neuron damage in stroke.…”