Bashir A Yousef1, Hozeifa M Hassan2, Lu-Yong Zhang3, Zhen-Zhou Jiang4. 1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Jiangsu Province, Nanjing 210009, PR China; Department of Pharmacology, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan. Electronic address: bashiralsiddiq@outlook.com. 2. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Jiangsu Province, Nanjing 210009, PR China; Department of Pharmacology, Faculty of Pharmacy, University of Gezira, Wad-Medani, Sudan. 3. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Jiangsu Province, Nanjing 210009, PR China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, PR China; Center for Drug Screening and Pharmacodynamics Evaluation, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. 4. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Jiangsu Province, Nanjing 210009, PR China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, PR China. Electronic address: beaglejiang@cpu.edu.cn.
Abstract
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-κB (NF-κB) 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-κB 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, IкB-α degradations and IкB-α phosphorylation in both dose- and time- dependent manners, which caused suppression of NF-кB p65 phosphorylation, nuclear translocation and accumulation of NF-кB. Moreover, pristimerin was found to inhibit both constitutive activated-NF-кB and tumor necrosis factor-α (TNF-α)- and lipopolysaccharide (LPS)-induced activation of NF-кB signaling pathway. Furthermore, our in vivo results on xenograft animal model revealed that pristimerin inhibited tumor growth mainly through suppressing NF-кB activity in tumor tissues. CONCLUSION: Pristimerin antitumor activities were mainly mediated through inhibition of NF-кB signaling pathway in colon tumor cells. These findings further explain that pristimerin has the therapeutic potential for targeting colon cancer.
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-κB (NF-κB) 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-κB 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, IкB-α degradations and IкB-α phosphorylation in both dose- and time- dependent manners, which caused suppression of NF-кB p65 phosphorylation, nuclear translocation and accumulation of NF-кB. Moreover, pristimerin was found to inhibit both constitutive activated-NF-кB and tumor necrosis factor-α (TNF-α)- and lipopolysaccharide (LPS)-induced activation of NF-кB signaling pathway. Furthermore, our in vivo results on xenograft animal model revealed that pristimerin inhibited tumor growth mainly through suppressing NF-кB activity in tumor tissues. CONCLUSION: Pristimerin antitumor activities were mainly mediated through inhibition of NF-кB signaling pathway in colon tumor cells. These findings further explain that pristimerin has the therapeutic potential for targeting colon cancer.
Authors: Elaine C D Gonçalves; Gabriela M Baldasso; Maíra A Bicca; Rodrigo S Paes; Raffaele Capasso; Rafael C Dutra Journal: Molecules Date: 2020-03-29 Impact factor: 4.411