Junshan Liu1, Xiduan Wei1, Yafeng Wu2, Yanni Wang1, Yuwen Qiu3, Junmin Shi4, Hongling Zhou1, Zibin Lu1, Meng Shao5, Linzhong Yu6, Li Tong7. 1. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. 2. Inpatient Department, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China. 3. Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China. 4. Southern Institute of Pharmaceutical Research, South China Normal University, Guangzhou, 510631, People's Republic of China. 5. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. sm326111@sina.com. 6. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. yulzh@smu.edu.cn. 7. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. zyxy2@smu.edu.cn.
Abstract
PURPOSE: Every year, almost one million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide and more than 690,000 patients die of it. At present, most therapeutic anti-HCC agents are not effective, which is due to the appearance of chemo-resistance and/or toxic side effects. Therefore, it is imperative to find novel more effective anti-HCC agents. Here, we evaluated the effect of giganteaside D (GD), an oleanolic acid saponin from P. scabiosaefolia, on the growth and apoptosis of HCC cells. METHODS AND RESULTS: Using MTT and clonogenic assays, we found that GD exhibited a significant growth inhibitory effect on the HCC-derived cell lines HepG2 and Bel-7402. In addition, we found that GD induced mitochondria-mediated apoptosis in these HCC-derived cells, as indicated by a decreased mitochondrial potential, activation of Caspase-9 and Caspase-3, cleavage of PARP and release of Cytochrome C from the mitochondria. Besides, we found that GD stimulated the generation of reactive oxygen species (ROS) and that blockage of ROS attenuated the GD-induced mitochondria-mediated apoptosis. Additionally, we found that GD treatment led to a decrease in phosphorylated Erk (p-Erk) and triggered the generation of p-JNK, both components of the mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of Erk or JNK by specific inhibitors or siRNAs augmented or attenuated the cytotoxic and apoptotic effects of GD. CONCLUSIONS: From our results we conclude that GD can induce ROS-mediated apoptosis in HCC-derived cells through the MAPK pathway. This observation may open up avenues to explore the future use of GD as a HCC chemotherapeutic agent.
PURPOSE: Every year, almost one million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide and more than 690,000 patients die of it. At present, most therapeutic anti-HCC agents are not effective, which is due to the appearance of chemo-resistance and/or toxic side effects. Therefore, it is imperative to find novel more effective anti-HCC agents. Here, we evaluated the effect of giganteaside D (GD), an oleanolic acid saponin from P. scabiosaefolia, on the growth and apoptosis of HCC cells. METHODS AND RESULTS: Using MTT and clonogenic assays, we found that GD exhibited a significant growth inhibitory effect on the HCC-derived cell lines HepG2 and Bel-7402. In addition, we found that GD induced mitochondria-mediated apoptosis in these HCC-derived cells, as indicated by a decreased mitochondrial potential, activation of Caspase-9 and Caspase-3, cleavage of PARP and release of Cytochrome C from the mitochondria. Besides, we found that GD stimulated the generation of reactive oxygen species (ROS) and that blockage of ROS attenuated the GD-induced mitochondria-mediated apoptosis. Additionally, we found that GD treatment led to a decrease in phosphorylated Erk (p-Erk) and triggered the generation of p-JNK, both components of the mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of Erk or JNK by specific inhibitors or siRNAs augmented or attenuated the cytotoxic and apoptotic effects of GD. CONCLUSIONS: From our results we conclude that GD can induce ROS-mediated apoptosis in HCC-derived cells through the MAPK pathway. This observation may open up avenues to explore the future use of GD as a HCC chemotherapeutic agent.
Entities:
Keywords:
Giganteaside D; Hepatocellular carcinoma; Mitochondrial apoptosis; Mitogen activated protein kinase; Reactive oxygen species
Authors: Felix H Shek; Ruibang Luo; Brian Y H Lam; Wing Kin Sung; Tak-Wah Lam; John M Luk; Ming Sum Leung; Kin Tak Chan; Hector K Wang; Chung Man Chan; Ronnie T Poon; Nikki P Lee Journal: Cell Oncol (Dordr) Date: 2017-06-19 Impact factor: 6.730