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Pristimerin exhibits in vitro and in vivo anticancer activities through inhibition of nuclear factor-small ka, CyrillicB signaling pathway in colorectal cancer cells.

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成果类型:
期刊论文
作者:
Yousef, Bashir A;Hassan, Hozeifa M;Zhang, LuYong;Jiang, ZhenZhou
通讯作者:
[Yousef, Bashir A;bashiralsiddiq@outlook.com]Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan. Electronic address:^[Jiang, Zhen-Zhou;beaglejiang@cpu.edu.cn]Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, PR China. Electronic address:
作者机构:
[Jiang, ZhenZhou; Zhang, LuYong; Hassan, Hozeifa M; Yousef, Bashir A] Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Jiangsu Province, Nanjing 210009, PR China
[Jiang, ZhenZhou] Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, PR China. Electronic address: beaglejiang@cpu.edu.cn
[Zhang, LuYong] Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, PR China
[Zhang, LuYong] Center for Drug Screening and Pharmacodynamics Evaluation, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China
[Hassan, Hozeifa M] Department of Pharmacology, Faculty of Pharmacy, University of Gezira, Wad-Medani, Sudan
语种:
英文
期刊:
Phytomedicine : international journal of phytotherapy and phytopharmacology
年:
2018
卷:
40
页码:
140-147
入藏号:
PMID:29496166
机构署名:
本校为其他机构
院系归属:
药学院
摘要:
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies associated with high mortality rate worldwide. We previously reported that pristimerin inhibits cell growth and induces apoptosis in CRC cells. HYPOTHESIS/PURPOSE: To further understand the molecular mechanism by which pristimerin elicits its anticancer activities on colon cancer cells, we investigated its effect on nuclear factor-kappaB (NF-kappaB) signaling pathway. STUDY DESIGN: This study consisted of both in vitro and in vivo experiments involving HCT-116 cell line and xenograft mouse model. Molecular techniques such as qRT-PCR, western blotting and immunofluorescence were used to demonstrate pristimerin in vitro effect on NF-kappaB signaling pathway; whereas it's in vivo activity was analyzed by western blot and immunohistochemistry on tumor tissues. RESULTS: Our in vitro results on HCT-116 cells showed that pristimerin inhibited IKK phosphorylation, Ismall ka, CyrillicB-alpha degradations and Ismall ka, CyrillicB-alpha phosphorylation in both dose- and time- dependent manners, which caused suppression of NF-small ka, CyrillicB p65 phosphorylation, nuclear translocation and accumulation of NF-small ka, CyrillicB. Moreover, pristimerin was found to inhibit both constitutive activated-NF-small ka, CyrillicB and tumor necrosis factor-alpha (TNF-alpha)- and lipopolysaccharide (LPS)-induced activation of NF-small ka, CyrillicB signaling pathway. Furthermore, our in vivo results on xenograft animal model revealed that pristimerin inhibited tumor growth mainly through suppressing NF-small ka, CyrillicB activity in tumor tissues. CONCLUSION: Pristimerin antitumor activities were mainly mediated through inhibition of NF-small ka, CyrillicB signaling pathway in colon tumor cells. These findings further explain that pristimerin has the therapeutic potential for targeting colon cancer.

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