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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 2734976, 16 pages
https://doi.org/10.1155/2017/2734976
Research Article

Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin

1Departamento de Bioquímica y Sección de Graduados, Escuela Superior de Medicina del IPN, Ciudad de México, Mexico
2CONACYT, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez, OAX, Mexico
3Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, Mexico

Correspondence should be addressed to José Guadalupe Trujillo-Ferrara; xm.npi@ollijurtj and Verónica Rocío Vásquez-Garzón; xm.tycanoc@agzeuqsavrv

Received 22 February 2017; Revised 12 June 2017; Accepted 18 July 2017; Published 10 October 2017

Academic Editor: Christian Widmann

Copyright © 2017 Gabriela Carrasco-Torres et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The inflammatory condition of malignant tumors continually exposes cancer cells to reactive oxygen species, an oxidizing condition that leads to the activation of the antioxidant defense system. A similar activation occurs with glutathione production. This oxidant condition enables tumor cells to maintain the energy required for growth, proliferation, and evasion of cell death. The objective of the present study was to determine the effect on hepatocellular carcinoma cells of a combination treatment with maleic anhydride derivatives (prooxidants) and quercetin (an antioxidant). The results show that the combination of a prooxidant/antioxidant had a cytotoxic effect on HuH7 and HepG2 liver cancer cells, but not on either of two normal human epithelial cell lines or on primary hepatocytes. The combination treatment triggered apoptosis in hepatocellular carcinoma cells by activating the intrinsic pathway and causing S phase arrest during cell cycle progression. There is also clear evidence of a modification in cytoskeletal actin and nucleus morphology at 24 and 48 h posttreatment. Thus, the current data suggest that the combination of two anticarcinogenic drugs, a prooxidant followed by an antioxidant, can be further explored for antitumor potential as a new treatment strategy.