Areca nut extract induced oxidative stress and upregulated hypoxia inducing factor leading to autophagy in oral cancer cells
Resource
AUTOPHAGY, 6(6), 725-737
Journal
Autophagy
Journal Volume
6
Journal Issue
6
Pages
725-737
Date Issued
2010
Date
2010
Author(s)
Lu, Hsuan-Hsuan
Kao, Shou-Yen
Liu, Tsung-Yun
Liu, Shou-Tien
Chang, Kuo-Wei
Lin, Shu-Chun
Abstract
Areca (betel) chewing was tightly linked to oral tumorigenesis in Asians. Areca nut was a recently confirmed group I carcinogen and a popular addictive substance used by Asians. Meanwhile, the pathogenetic impact of areca on oral epithelial cells was still unclear. This study investigated the association between the induction of autophagy by areca nut extract (ANE) and the molecular regulation underlying this induction in oral cancer cells. Oral cancer cells were treated with ANE to incite the signaling changes underlying phenotypic alterations. The NFκB activation and reactive oxygen species (ROS) genesis were induced by ANE and the NFκB activation could be the basis of the ROs genesis. Furthermore, p38 activation and upregulation of MKP-1 phosphatase occurred following ANE treatment. These effects can be inhibited by ROS blockers. ANE treatment induced autophagy among oral cancer cells, which was characterized by LC3-II accumulation, genesis of autophagosomes and the appearance of EGFP-LC3 puncta. This induction was mediated through the activation of p38, MKP-1 and HIF-1α. Knockdown of ANE-modulated HIF-1α expression reduced autophagy. Blockage of ANE-induced autophagy increased the proportion of oral cancer cells undergoing apoptotic death. This study identified for the first time that ANE modulates a signaling cascade that induces HIF-1α expression in oral cancer cells. The eventual induction of autophagy was beneficial to cell survival from ANE-induced apoptosis. ? 2010 Landes Bioscience.
Subjects
Areca; Autophagy; HIF-1α; MKP-1; Oral cancer; ROS
SDGs
Other Subjects
glyceraldehyde 3 phosphate dehydrogenase; hypoxia inducible factor; hypoxia inducible factor 1alpha; immunoglobulin enhancer binding protein; membrane protein; mitogen activated protein kinase; mitogen activated protein kinase kinase 6; mitogen activated protein kinase p38; protein LC3 II; protein Mkp 1; protein p50; reactive oxygen metabolite; synaptotagmin I; unclassified drug; apoptosis; article; Asian; autophagosome; autophagy; betel nut; bioaccumulation; carcinogenesis; cell survival; controlled study; enzyme activation; human; human cell; mastication; mouth cancer; nonhuman; oral tumorigenesis; oxidative stress; phagosome; phenotype; protein expression; signal transduction; upregulation; Areca; Areca catechu; Piper betel
Type
journal article
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