title: Total alkaloids of Tripterygium hypoglaucum (levl.) Hutch inhibits tumor growth both in vitro and in vivo.
abstract: BACKGROUND
  Tripterygium hypoglaucum (levl.) Hutch (Celastraceae) (THH) root is a traditional Chinese medicinal herb commonly used for treating autoimmune diseases and cancer. Alkaloid is one of the most bioactive components of THH extract. To evaluate the in vitro and in vivo antitumor properties of the total alkaloids of THH (THHta).
  
  
  METHODS
  THHta was extracted in pilot-scale. HCT116 cells were chose to establish human colon cancer xenograft model. The in vitro anti-tumor activity of THHta was tested by Cell malignant transformation test, Soft agar colony formation assay and MTT assay. The in vivo anti-tumor effect of THHta was confirmed by xenograft mouse model. THHta-induced apoptosis was examined by flow cytometry. The levels of apoptosis-related proteins were investigated by Western blot.
  
  
  RESULTS
  TPA-induced cell transformation was significantly inhibited by THHta in JB6 Cl41 cells. THHta inhibits the growth of colon cancer cells in vitro in a significant dose-dependent manner. Compared to the control set, i.p. administration of THHta to xenograft mice signiﬁcantly reduced both tumor weight and volume. Apoptosis induction of THHta was mediated by activation of caspase-3, PARP and inhibiting of Bcl-2, Bcl-xL and XIAP.
  
  
  CONCLUSIONS
  THHta was effective in inhibiting tumor growth both in vitro and in vivo at less toxic concentrations by inducing apoptosis which suggested it could be developed as a potential anticancer agent.
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Huang
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ao
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
authors.forename: Wen-bin
authors.initials: WB
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
authors.forename: Dong-yun
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
authors.forename: Chuan-shu
authors.initials: CS
authors.lastname: Huang
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China. Electronic address: jinyiliutmmu@163.com.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D018517:Plant Roots / Q000737:chemistry; D029757:Tripterygium / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents
keywords: 12-O-tetradecanog 1 phorbol-13-acetate; Alkaloid; Apoptosis; B-cell lymphoma 2; B-cell lymphoma-extra large; Bcl-2; Bcl-xL; DISC; DMSO; FADD; FBS; Fas associated death domain protein; HE; PARP; TBST; THH; THHta; TNF receptor associated death domain; TPA; TRADD; Traditional Chinese medicine; Tripterygium hypoglaucum (levl.) Hutch; Tripterygium hypoglaucum (levl.) Hutch (Celastraceae); Tris Buffered Saline Tween; X-linked inhibitor of apoptosis protein; XIAP; death-inducing signaling complex; dimethyl sulfoxide; fetal bovine serum; hematoxylin and eosin; poly ADP-ribose polymerase; total alkaloids of Tripterygium hypoglaucum (levl.) Hutch (Celastraceae)