TY - JOUR
T1 - Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin
AU - Carrasco-Torres, Gabriela
AU - Baltiérrez-Hoyos, Rafael
AU - Andrade-Jorge, Erik
AU - Villa-Treviño, Saúl
AU - Trujillo-Ferrara, José Guadalupe
AU - Vásquez-Garzón, Verónica Rocío
N1 - Publisher Copyright:
© 2017 Gabriela Carrasco-Torres et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042604828&partnerID=8YFLogxK
U2 - 10.1155/2017/2734976
DO - 10.1155/2017/2734976
M3 - Artículo
C2 - 29163752
SN - 1942-0900
VL - 2017
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 2734976
ER -