An ortho-carbonyl substituted hydroquinone derivative is an anticancer agent that acts by inhibiting mitochondrial bioenergetics and by inducing G₂/M-phase arrest in mammary adenocarcinoma TA3

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• 作者：Fé ; lix A. Urra^a ; ^{felix.urra@qf.uchile.cl} ; Maximiliano Martí ; nez-Cifuentes^a ; Mario Pavani^b ; Michel Lapier^b ; Fabiá ; n Jañ ; a-Prado^b ; Eduardo Parra^c ; Juan Diego Maya^b ; Herná ; n Pessoa-Mahana^a ; Jorge Ferreira^b ; ^{jferreir@med.uchile.cl} ; Ramiro Araya-Maturana^a ; ^{raraya@ciq.uchile.cl}
• 关键词：Mitochondrial bioenergetics ; Cancer ; Oxidative phosphorylation ; Anticancer agents ; Cell cycle arrest ; Mitochondria ; Hydroquinone
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2013
• 出版时间：15 March, 2013
• 年：2013
• 卷：267
• 期：3
• 页码：218-227
• 全文大小：718 K

文摘

Tumor cells present a known metabolic reprogramming, which makes them more susceptible for a selective cellular death by modifying its mitochondrial bioenergetics. Anticancer action of the antioxidant 9,10-dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one (HQ) on mouse mammary adenocarcinoma TA3, and its multiresistant variant TA3-MTXR, were evaluated. HQ decreased the viability of both tumor cells, affecting slightly mammary epithelial cells. This hydroquinone blocked the electron flow through the NADH dehydrogenase (Complex I), leading to ADP-stimulated oxygen consumption inhibition, transmembrane potential dissipation and cellular ATP level decrease, without increasing ROS production. Duroquinol, an electron donor at CoQ level, reversed the decrease of cell viability induced by HQ. Additionally, HQ selectively induced G₂/M-phase arrest. Taken together, our results suggest that the bioenergetic dysfunction provoked by HQ is implicated in its anticancer action.