Isorhamnetin Inhibits Reactive Oxygen Species-Dependent Hypoxia Inducible Factor (HIF)-1α Accumulation.
Isorhamnetin is a flavonoid metabolite of quercetin and isolated from water dropwort (Oenanthe javanica, Umbelliferae). It has been reported that isorhamnetin exerts beneficial effects including antioxidant, anti-inflammatory, and anti-proliferative activities. The present study investigated whether the antioxidant activity of isorhamnetin is correlated with its anti-cancer effects on colorectal cancer cells. Isorhamnetin significantly repressed cobalt chloride (CoCl2)- or hypoxia-induced hypoxia inducible factor-1α (HIF-1α) accumulation in HCT116 and HT29 cells. When compared with quercetin, isorhamnetin showed potent inhibition of HIF-1α. Moreover, it inhibited CoCl2-induced activity of hypoxia response element reporter gene and HIF-1α-dependent transcription of genes such as glucose transporter 1, lactate dehydrogenase A, carbonic anhydrase-IX, and pyruvate dehydrogenase kinase 1. Isorhamnetin also blocked hydrogen peroxide (H2O2)-induced HIF-1α accumulation. The antioxidant effects of isorhamnetin were confirmed by observation of CoCl2- or H2O2-induced reactive oxygen species (ROS) production. Consistently, overexpressed HIF-1α was decreased by isorhamnetin or N-acetyl-L-cysteine in HEK293 cells. In vitro migration and invasion assay further confirmed the inhibitory effects of isorhamnetin on cancer cells. Collectively, these results demonstrate that isorhamnetin inhibits ROS-mediated HIF-1α accumulation, which contributes to its anti-metastatic efficacy.
College of Pharmacy, Chosun University.
Suho
S
Seo
Kyuhwa
K
Seo
Sung Hwan
SH
Ki
Sang Mi
SM
Shin
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D003035:Cobalt; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; C047368:3-methylquercetin; D003035:Cobalt; D011794:Quercetin; C018021:cobaltous chloride