PMID- 30878505
OWN - NLM
STAT- MEDLINE
DCOM- 20200413
LR  - 20200413
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 370
DP  - 2019 May 1
TI  - Resveratrol inhibits cancer cell proliferation by impairing oxidative 
      phosphorylation and inducing oxidative stress.
PG  - 65-77
LID - S0041-008X(19)30090-0 [pii]
LID - 10.1016/j.taap.2019.03.008 [doi]
AB  - 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 (IC(50) = 200-250 muM) cells than of low metastatic 
      MCF-7, SiHa and A549 (IC(50) = 400-500 muM) and non-cancer HUVEC and 3T3 
      (IC(50)>/=600 muM) cells after 48 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 muM/48 h) significantly decreased both glycolysis and 
      oxidative phosphorylation (OxPhos) protein contents (30-90%) and fluxes (40-70%) 
      vs. non-treated cells. RSV (100 muM/1-5 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 muM/48 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.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico. Electronic 
      address: sara.rodriguez@cardiologia.org.mx.
FAU - Pacheco-Velazquez, Silvia Cecilia
AU  - Pacheco-Velazquez SC
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Marin-Hernandez, Alvaro
AU  - Marin-Hernandez A
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Gallardo-Perez, Juan Carlos
AU  - Gallardo-Perez JC
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Robledo-Cadena, Diana Xochiquetzal
AU  - Robledo-Cadena DX
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Hernandez-Resendiz, Ileana
AU  - Hernandez-Resendiz I
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Garcia-Garcia, Jorge Donato
AU  - Garcia-Garcia JD
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Belmont-Diaz, Javier
AU  - Belmont-Diaz J
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Lopez-Marure, Rebeca
AU  - Lopez-Marure R
AD  - Departamento de Fisiologia, Instituto Nacional de Cardiologia, Mexico.
FAU - Hernandez-Esquivel, Luz
AU  - Hernandez-Esquivel L
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Sanchez-Thomas, Rosina
AU  - Sanchez-Thomas R
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico.
FAU - Moreno-Sanchez, Rafael
AU  - Moreno-Sanchez R
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico. Electronic 
      address: rafael.moreno@cardiologia.org.mx.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190313
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Phytochemicals)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - HeLa Cells
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - MCF-7 Cells
MH  - Mice
MH  - Mitophagy/drug effects
MH  - Neoplasm Metastasis/prevention & control
MH  - Neoplasms/*pathology
MH  - Oxidative Phosphorylation/*drug effects
MH  - Oxidative Stress/*drug effects
MH  - Phytochemicals/pharmacology
MH  - Resveratrol/*pharmacology
OTO - NOTNLM
OT  - Antioxidant response
OT  - Cancer
OT  - Mitophagy
OT  - Oxidative phosphorylation
OT  - ROS production
EDAT- 2019/03/18 06:00
MHDA- 2020/04/14 06:00
CRDT- 2019/03/18 06:00
PHST- 2018/11/19 00:00 [received]
PHST- 2019/03/05 00:00 [revised]
PHST- 2019/03/11 00:00 [accepted]
PHST- 2019/03/18 06:00 [pubmed]
PHST- 2020/04/14 06:00 [medline]
PHST- 2019/03/18 06:00 [entrez]
AID - S0041-008X(19)30090-0 [pii]
AID - 10.1016/j.taap.2019.03.008 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2019 May 1;370:65-77. doi: 10.1016/j.taap.2019.03.008. 
      Epub 2019 Mar 13.