Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo

• Published in: Cancer letters Vol. 319; no. 2; pp. 203 - 213
• Main Authors: Li, Chia-Jung, Chu, Ching-Yu, Huang, Lin-Huang, Wang, Ming-Hseng, Sheu, Lai-Fa, Yeh, Jih-I, Hsu, Hsue-Yin
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Limited 28.06.2012
• Subjects: Animal models; Animals; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Apoptosis; Apoptosis - drug effects; Cancer therapies; Caspase-3; Cell culture; Cell growth; Cell Line, Tumor; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cytochrome c; Cytotoxicity; Deoxyribonucleic acid; Diterpenes - administration & dosage; DNA; DNA damage; DNA repair; Drug dosages; Drug Synergism; Epoxy Compounds - administration & dosage; Gastric cancer; Hematology, Oncology and Palliative Medicine; Herbal medicines; Humans; Male; Membrane potential; Mice; Mice, SCID; Mitochondria; Mortality; Phenanthrenes - administration & dosage; Phytotherapy - methods; Plant Extracts; Proliferating cell nuclear antigen; Severe combined immunodeficiency; Side effects; Stomach Neoplasms - drug therapy; Studies; Therapeutic applications; Toxicity; Tripterygium; triptolide; Tumors; Xenograft Model Antitumor Assays; Xenografts; Xenograft; Synergism; Mitochondrial apoptotic pathway; Triptolide; Cisplatin
• DOI: 10.1016/j.canlet.2012.01.006
• ISSN: 0304-3835

Abstract Cisplatin is an anticancer agent that is effective against several types of cancer, including gastric cancer. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to clarify how triptolide, an active component extracted from the traditional Chinese herbal medicine Tripterygium wilfordii Hook F (TWHF), enhances cisplatin-induced cytotoxicity in gastric cancer SC-M1 cells. After low-dose combined treatments with triptolide and cisplatin, a decrease in viability with a concomitant increase in apoptosis was observed in SC-M1 cells but not in normal cells. Apoptosis induced by the combined treatments was accompanied by loss of mitochondrial membrane potential and release of cytochrome c . Triptolide increased the cisplatin-induced activation of caspase-3 and caspase-9 and the downstream cleavage of PARP in SC-M1 cells. Results of these in vitro experiments indicated that triptolide enhanced cytotoxicity in cisplatin-treated SC-M1 cells and that this effect is mediated by apoptosis through a mitochondrial pathway. Furthermore, using a SCID mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumor growth via down-regulation of proliferating cell nuclear antigen expression without significant side effects. These results suggest that lower concentrations of cisplatin and triptolide used in combination may produce a synergistic anticancer effect that warrants further investigation for its potential clinical applications.