Yuhua Li1, Changxu Liu2, Dan Xiao3, Jing Han4, Zhenggang Yue4, Yang Sun4, Lei Fan4, Feng Zhang4, Jin Meng5, Rong Zhang4, Zhipeng Wang4, Qibing Mei6, Aidong Wen7. 1. 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. 2. No. 422 Hospital of PLA, Zhanjiang 524005, Guangdong, PR China. 3. Department of epidemiology, School of public health, the Fourth military medical university, Xi'an 710032, Shaanxi, PR China. 4. 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. 5. Department of Pharmacy, No. 309 Hospital of PLA, Beijing 100000, PR China. 6. 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. 7. Department of Pharmacy, Xijing Hospital, the Fourth military medical university, Xi'an 710032, Shaanxi, PR China. Electronic address: yuhualee973@aliyun.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Saponins of many herbs are known to possess anti-cancer effect. AIM OF THE STUDY: 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. MATERIALS AND 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. CONCLUSION: These data suggest that TTS has a potential role in clinical prevention and treatment for colorectal cancer.
ETHNOPHARMACOLOGICAL RELEVANCE: Saponins of many herbs are known to possess anti-cancer effect. AIM OF THE STUDY: 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 humancolorectal cancer cell line HT-29, and isolate some major constituents and evaluate their anti-tumor activity. MATERIALS AND 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. CONCLUSION: These data suggest that TTS has a potential role in clinical prevention and treatment for colorectal cancer.
Authors: Shafiq Ur Rahman; Achyut Adhikari; Muhammad Ismail; Muhammad Raza Shah; Muhammad Khurram; Muhammad Shahid; Farman Ali; Abdul Haseeb; Fazal Akbar; Marcello Iriti Journal: Molecules Date: 2016-08-20 Impact factor: 4.411