title: 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.
abstract: 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.
authors: Department of Organic and Physical Chemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone 1007, Casilla 233, Santiago-1, Chile. felix.urra@qf.uchile.cl
authors: Félix A
authors: FA
authors: Urra
authors: Maximiliano
authors: M
authors: Martínez-Cifuentes
authors: Mario
authors: M
authors: Pavani
authors: Michel
authors: M
authors: Lapier
authors: Fabián
authors: F
authors: Jaña-Prado
authors: Eduardo
authors: E
authors: Parra
authors: Juan Diego
authors: JD
authors: Maya
authors: Hernán
authors: H
authors: Pessoa-Mahana
authors: Jorge
authors: J
authors: Ferreira
authors: Ramiro
authors: R
authors: Araya-Maturana
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D006873:Hydroquinones; C016421:duroquinol; C031927:hydroquinone