Butin (7,3′,4′-trihydroxydihydroflavone) reduces oxidative stress-induced cell death via inhibition of the mitochondria-dependent apoptotic pathway

Rui Zhang, In Kyung Lee, Mei Jing Piao, Ki Cheon Kim, Areum Daseul Kim, Hye Sun Kim, Sungwook Chae, Hee Sun Kim, Jin Won Hyun

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8 Scopus citations

Abstract

Recently, we demonstrated that butin (7,3′,4′-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H 2O 2)-induced apoptosis by: (1) scavenging reactive oxygen species (ROS), activating antioxidant enzymes such superoxide dismutase and catalase; (2) decreasing oxidative stress-induced 8-hydroxy-2′-deoxyguanosine levels via activation of oxoguanine glycosylase 1, and (3), reducing oxidative stress-induced mitochondrial dysfunction. The objective of this study was to determine the cytoprotective effects of butin on oxidative stress-induced mitochondria-dependent apoptosis, and possible mechanisms involved. Butin significantly reduced H 2O 2-induced loss of mitochondrial membrane potential as determined by confocal image analysis and flow cytometry, alterations in Bcl-2 family proteins such as decrease in Bcl-2 expression and increase in Bax and phospho Bcl-2 expression, release of cytochrome c from mitochondria into the cytosol and activation of caspases 9 and 3. Furthermore, the anti-apoptotic effect of butin was exerted via inhibition of mitogen-activated protein kinase kinase-4, c-Jun NH2-terminal kinase (JNK) and activator protein-1 cascades induced by H 2O 2 treatment. Finally, butin exhibited protective effects against H 2O 2-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G 1 hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H 2O 2-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway.

Original languageEnglish
Pages (from-to)3871-3887
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume12
Issue number6
DOIs
StatePublished - 1 Jun 2011

Keywords

  • Butin
  • Mitochondria-dependent apoptotic pathway
  • Oxidative stress

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