title: Trillium tschonoskii steroidal saponins suppress the growth of colorectal Cancer cells in vitro and in vivo.
abstract: BACKGROUND
  Saponins of many herbs are known to possess anti-cancer effect.
  
  
  OBJECTIVE
  The present study aimed to investigate the growth inhibitory effect of Trillium tschonoskii steroidal saponins in a mouse model of colitis-associated colorectal cancer and a human colorectal cancer cell line HT-29, and isolate some major constituents and evaluate their anti-tumor activity.
  
  
  METHODS
  Forty male ICR mice were administered with 1, 2-dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Ten mice were given no further treatment, the rest were administered with different doses of TTS (5, 10, 20mg/kg) orally, every three days from the 9th week to the 20th week.
  
  
  RESULTS
  TTS effectively protected ICR mice against DMH/DSS-induced tumorigenesis. The incidence of tumor development was 90% (9/10) in the mice treated with DMH/DSS, but that was reduced to 50% (5/10), 40% (4/10), and 20% (2/10), respectively, in the mice treated with 5%, 10%, and 20% of TTS. Results of Ki-67 staining, TUNEL assay and caspase-3 activity assay revealed that TTS moderately decreased abnormal proliferation and increased apoptosis of colonic epithelial cells. It inhibited the growth and triggered the apoptosis of HT-29 cells, partly through suppressing mitogen-actived protein kinases (MAPKs) and triggering mitochondrial-mediated apoptotic pathway. Three compounds, namely, Paris saponin VII, polyphylloside III and Paris saponin VI, were important active compounds in TTS.
  
  
  CONCLUSIONS
  These data suggest that TTS has a potential role in clinical prevention and treatment for colorectal cancer.
authors: Department of Pharmacy, Xijing Hospital, the Fourth military medical university, Xi'an 710032, Shaanxi, PR China; No. 422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China.
authors: Yuhua
authors: Y
authors: Li
authors: No. 422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China.
authors: Changxu
authors: C
authors: Liu
authors: Department of epidemiology, School of public health, the Fourth military medical university, Xi'an 710032, Shaanxi, PR China.
authors: Dan
authors: D
authors: Xiao
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors: Jing
authors: J
authors: Han
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors: Zhenggang
authors: Z
authors: Yue
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors: Yang
authors: Y
authors: Sun
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors: Lei
authors: L
authors: Fan
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors: Feng
authors: F
authors: Zhang
authors: Department of Pharmacy, No. 309 Hospital of PLA, Beijing 100000, PR China.
authors: Jin
authors: J
authors: Meng
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors: Rong
authors: R
authors: Zhang
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors: Zhipeng
authors: Z
authors: Wang
authors: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China. Electronic address: qbmei53@hotmail.com.
authors: Qibing
authors: Q
authors: Mei
authors: Department of Pharmacy, Xijing Hospital, the Fourth military medical university, Xi'an 710032, Shaanxi, PR China. Electronic address: yuhualee973@aliyun.com.
authors: Aidong
authors: A
authors: Wen
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D016264:Dextran Sulfate; D019073:HT29 Cells; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use*; D031446:Trillium
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D016264:Dextran Sulfate; D020928:Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D019813:1,2-Dimethylhydrazine
keywords: Apoptosis; Growth inhibition; Mitogen-actived protein kinases (MAPKs); Trillium tschonoskii steroidal saponins (TTS)