title: Evaluation of the effects of the water-soluble total flavonoids from Isodon lophanthoides var.gerardianus (Benth.) H. Hara on apoptosis in HepG2 cell: Investigation of the most relevant mechanisms.
abstract: BACKGROUND
  The water-soluble total flavonoids (WSTF) were extracted from Isodon lophanthoides var. gerardianus (Benth.) H. Hara, a common folk herbal medicine in China, which has been recorded by the "Chinese Pharmacopoeia" in 2015 and used for prevention and clinical treatment of common diseases of liver and gall for many years.
  
  
  OBJECTIVE
  The aim of this study is to evaluate the effects of WSTF on apoptosis in HepG2 cell and investigate the relevant mechanisms underlying.
  
  
  METHODS
  Cytotoxicity was evaluated in HepG2 cells (human hepatoma cell lines) using MTT assay. The influence of the WSTF on the intracellular reactive oxygen species (iROS) and the mitochondrial membrane potential were also determinated. We used flow cytometry analysis to detect the effects of WSTF on apoptosis, cell cycle. Then we applied RT-PCR for genetic expression of main effectors and western blot analysis for activation of main effectors involved in the potential apoptosis signaling pathways.
  
  
  RESULTS
  WSTF inhibited cell growth in HepG2 cells. Moreover, WSTF stimulates to increase amount of iROS, mitochondrial membrane potential, and the apoptotic relevant factors (cytochrome c, caspase-3) in HepG2 cells. WSTF could significantly induce apoptosis through downregulating apoptosis-antagonizing protein (Bcl-2, Survivin, mcl-1) and upregulating apoptosis-promoting proteins (Bax) and cell cycle G0/G1 arrest in HepG2 cells.
  
  
  CONCLUSIONS
  The results indicate that WSTF induces cell apoptosis through mitochondrial pathway in the HepG2 cells. Therefore, these studies suggest that WSTF could be used as a chemotherapeutic agent to treat hepatoma.
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Waihuandong Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China; Department of Pharmacy, Hunan Traditional Chinese Medical College, lusong Road No. 136, Zhuzhou 412012, China. Electronic address: everyday76@163.com.
authors.forename: Chuan-Ping
authors.initials: CP
authors.lastname: Feng
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Waihuandong Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. Electronic address: thm1835@qq.com.
authors.forename: Hai-Ming
authors.initials: HM
authors.lastname: Tang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Waihuandong Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. Electronic address: huangnn421@163.com.
authors.forename: Song
authors.initials: S
authors.lastname: Huang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Waihuandong Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. Electronic address: 329022681@qq.com.
authors.forename: Shao-Zhen
authors.initials: SZ
authors.lastname: Hou
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Waihuandong Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. Electronic address: 451687820@qq.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Waihuandong Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. Electronic address: 791365195@qq.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Waihuandong Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. Electronic address: lxp88@gzhtcm.edu.cn.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D037602:Isodon / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012997:Solvents; D014867:Water
keywords: Cell apoptosis; Relevant mechanisms; The water-soluble total flavonoids from Isodon Lophanthoides var. gerardianus (Benth.) H. Hara