Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway.
Severe side effects and complications such as gastrointestinal and hematological toxicities because of current anticancer drugs are major problems in the clinical management of gastric cancer, which highlights the urgent need for novel effective and less toxic therapeutic approaches. Hispolon, an active polyphenol compound, is known to possess potent antineoplastic and antiviral properties. In this study, we investigated the efficacy of hispolon in human gastric cancer cells and explored the cell death mechanism. Hispolon induced ROS-mediated apoptosis in gastric cancer cells and was more toxic toward gastric cancer cells than toward normal gastric cells, suggesting greater susceptibility of the malignant cells. The mechanism of hispolon-induced apoptosis was that hispolon abrogated the glutathione antioxidant system and caused massive ROS accumulation in gastric cancer cells. Excessive ROS caused oxidative damage to the mitochondrial membranes and impaired the membrane integrity, leading to cytochrome c release, caspase activation, and apoptosis. Furthermore, hispolon potentiated the cytotoxicity of chemotherapeutic agents used in the clinical management of gastric cancer. These results suggest that hispolon could be useful for the treatment of gastric cancer either as a single agent or in combination with other anticancer agents.
Chen
Wei
W
College of Life Science, Zhejiang University, Hangzhou 310058, China.
Zhao
Zhao
Z
Li
Ling
L
Wu
Bin
B
Chen
Shi-fei
SF
Zhou
Hong
H
Wang
Yong
Y
Li
Yong-Quan
YQ
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000975:Antioxidants; D002396:Catechols; D017382:Reactive Oxygen Species; C103442:hispolon; D005978:Glutathione