Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine

// Qi-Wei Jiang 1, * , Ke-Jun Cheng 2, 3, * , Xiao-Long Mei 1 , Jian-Ge Qiu 1 , Wen-Ji Zhang 1 , You-Qiu Xue 1 , Wu-Ming Qin 1 , Yang Yang 1 , Di-Wei Zheng 1 , Yao Chen 1 , Meng-Ning Wei 1 , Xu Zhang 3 , Min Lv 4 , Mei-Wan Chen 5 , Xing Wei 1 , Zhi Shi 1 1 Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China 2 Chemical Biology Center, Lishui Institute of Agricultural Sciences, Lishui, Zhejiang, China 3 National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China 4 Institute of Materia Medica, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China 5 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China * These authors have contributed equally to this work. Correspondence to: Zhi Shi, e-mail: tshizhi@jnu.edu.cn Keywords: triptolide, celastrol, combination therapy, cancer Received: June 23, 2015      Accepted: September 25, 2015      Published: October 05, 2015 ABSTRACT Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo , suggesting that this beneficial combination may offer a promising treatment option for cancer patients.