title: Evaluation of the medicinal herb Graptopetalum paraguayense as a treatment for liver cancer.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Sorafenib is the only drug for patients with advanced-stage hepatocellular carcinoma (HCC) that has been shown to confer a survival benefit to patients with HCC; however, it has many side effects. Thus, alternate therapeutic strategies with improved safety and therapeutic efficacy for the management of HCC should be developed.
  
  
  RESULTS
  We demonstrate that an extract of Graptopetalum paraguayense (GP) down-regulated the expression levels of several onco-proteins, including AURKA, AURKB, and FLJ10540, in HCC cells. To isolate the active components in the GP extracts, we prepared extracts fractions and assessed their effects on the expression of onco-proteins in HCC cells. The fraction designated HH-F3 was enriched in active ingredients, exhibited cytotoxic effects, and suppressed the expression of the onco-proteins in HCC cells. The structure of the main active compound in HH-F3 was found to be similar to that of the proanthocyanidin compounds derived from Rhodiola rosea. In addition, a distinct new compound rich in 3, 4, 5-trihydroxy benzylic moieties was identified in the HH-F3 preparations. Mechanistic studies indicated that HH-F3 induced apoptosis in HCC cells by promoting the loss of mitochondrial membrane potential and the production of reactive oxygen species. HH-F3 also enhanced PTEN expression and decreased AKT phosphorylation at Ser473 in a concentration-dependent manner in HCC cells. Moreover combination of GP or HH-F3 and sorafenib synergistically inhibits the proliferation of Huh7 cells. The treatment of a rat model with diethylnitrosamine (DEN)-induced liver cancer with extracts of GP and HH-F3 decreased hepatic collagen contents and inhibited tumor growth.
  
  
  CONCLUSIONS
  These results indicate that GP extracts and HH-F3 can protect the liver by suppressing tumor growth; consequently, these compounds could be considered for the treatment of HCC.
authors: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors: Wei-Hsiang
authors: WH
authors: Hsu
authors: School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors: Chia-Chuan
authors: CC
authors: Chang
authors: Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors: Kai-Wen
authors: KW
authors: Huang
authors: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors: Yi-Chen
authors: YC
authors: Chen
authors: Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Shih-Lan
authors: SL
authors: Hsu
authors: Department of Applied Chemistry and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Nantou, Taiwan.
authors: Li-Chen
authors: LC
authors: Wu
authors: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Ann-Ping
authors: AP
authors: Tsou
authors: Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan.
authors: Jin-Mei
authors: JM
authors: Lai
authors: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan; Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chi-Ying F
authors: CY
authors: Huang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D031995:Saxifragaceae / Q000737:chemistry*
chemical_list: D009363:Neoplasm Proteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species