title: Giganteaside D induces ROS-mediated apoptosis in human hepatocellular carcinoma cells through the MAPK pathway.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: Junshan
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: Xiduan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Inpatient Department, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, People's Republic of China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Southern Institute of Pharmaceutical Research, South China Normal University, Guangzhou, 510631, People's Republic of China.
authors.forename: Junmin
authors.initials: J
authors.lastname: Shi
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: Zibin
authors.initials: Z
authors.lastname: Lu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. sm326111@sina.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Shao
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. yulzh@smu.edu.cn.
authors.forename: Linzhong
authors.initials: L
authors.lastname: Yu
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China. zyxy2@smu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Tong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032405:Patrinia / Q000737:chemistry; D008517:Phytotherapy / Q000379:methods; D018517:Plant Roots / Q000737:chemistry; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D014162:Transfection
chemical_list: C476672:3-O-alpha-L-rhamnopyranosyl-(1-2)-beta-D-xylopyranosyl oleanolic acid; D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012503:Saponins; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Giganteaside D; Hepatocellular carcinoma; Mitochondrial apoptosis; Mitogen activated protein kinase; Reactive oxygen species