Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo.
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.
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. Electronic address: 97751101@stmail.tcu.edu.tw.
Chia-Jung
CJ
Li
Department of Life Sciences, Tzu Chi University, Hualien, Taiwan. Electronic address: chingyu@mail.tcu.edu.tw.
Ching-Yu
CY
Chu
School of Medicine, Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: yg1236@yahoo.com.tw.
Lin-Huang
LH
Huang
Department of Life Sciences, Tzu Chi University, Hualien, Taiwan. Electronic address: wangmh@mail.tcu.edu.tw.
Ming-Hseng
MH
Wang
Department of Pathology, Buddhist Tzu Chi General Hospital Taichung Branch, Taichung, Taiwan. Electronic address: laifakimo@yahoo.com.tw.
Lai-Fa
LF
Sheu
Department of Family Medicine, Tzu Chi University, Hualien, Taiwan; Department of Family Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan. Electronic address: jihiyeh@mail.tcu.edu.tw.
Jih-I
JI
Yeh
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; Department of Life Sciences, Tzu Chi University, Hualien, Taiwan. Electronic address: hsueyin@mail.tcu.edu.tw.
Hsue-Yin
HY
Hsu
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D004224:Diterpenes / Q000008:administration & dosage*; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000008:administration & dosage; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010616:Phenanthrenes / Q000008:administration & dosage*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts; D013274:Stomach Neoplasms / Q000188:drug therapy*; D029757:Tripterygium; D023041:Xenograft Model Antitumor Assays
D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D010936:Plant Extracts; C001899:triptolide; D002945:Cisplatin