Resveratrol inhibits cancer cell proliferation by impairing oxidative phosphorylation and inducing oxidative stress.
Toxicol Appl Pharmacol
; 370: 65-77, 2019 05 01.
Article
em En
| MEDLINE
| ID: mdl-30878505
ABSTRACT
The resveratrol (RSV) efficacy to affect the proliferation of several cancer cell lines was initially examined. RSV showed higher potency to decrease growth of metastatic HeLa and MDA-MB-231 (IC50â¯=â¯200-250⯵M) cells than of low metastatic MCF-7, SiHa and A549 (IC50â¯=â¯400-500⯵M) and non-cancer HUVEC and 3T3 (IC50≥600⯵M) cells after 48â¯h exposure. In order to elucidate the biochemical mechanisms underlying RSV anti-cancer effects, the energy metabolic pathways and the oxidative stress metabolism were analyzed in HeLa cells as metastatic-type cell model. RSV (200⯵M/48â¯h) significantly decreased both glycolysis and oxidative phosphorylation (OxPhos) protein contents (30-90%) and fluxes (40-70%) vs. non-treated cells. RSV (100⯵M/1-5â¯min) also decreased at a greater extent OxPhos flux (net ADP-stimulated respiration) of isolated tumor mitochondria (> 50%) than of non-tumor mitochondria (< 50%), particularly with succinate as oxidizable substrate. In addition, RSV promoted an excessive cellular ROS (2-3 times) production corresponding with a significant decrement in the SOD activity (but not in its content) and GSH levels; whereas the catalase, glutahione reductase, glutathione peroxidase and glutathione-S-transferase activities (but not their contents) remained unchanged. RSV (200⯵M/48â¯h) also induced cellular death although not by apoptosis but rather by promoting a strong mitophagy activation (65%). In conclusion, RSV impaired OxPhos by inducing mitophagy and ROS over-production, which in turn halted metastatic HeLa cancer cell growth.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
Base de dados:
MEDLINE
Assunto principal:
Fosforilação Oxidativa
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Estresse Oxidativo
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Proliferação de Células
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Resveratrol
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Neoplasias
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Antineoplásicos Fitogênicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article