Cryptolepine Suppresses Colorectal Cancer Cell Proliferation, Stemness, and Metastatic Processes by Inhibiting WNT/β-Catenin Signaling

Author:

Quarshie Jude Tetteh1ORCID,Fosu Kwadwo1ORCID,Offei Nicholas Awuku1ORCID,Sobo Augustine Kojo1,Quaye Osbourne1ORCID,Aikins Anastasia Rosebud1ORCID

Affiliation:

1. West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry Cell and Molecular Biology, University of Ghana, Accra P.O. Box LG 54, Ghana

Abstract

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths globally. Evidence shows that over 90% of CRC cases are initiated by a deregulated Wingless Integrated Type-1 (WNT)/β-catenin signaling pathway. The WNT/β-catenin pathway also promotes CRC cell proliferation, stemness, and metastasis. Therefore, modulators of the WNT/β-catenin pathway may serve as promising regimens for CRC. This study investigated the effect of cryptolepine—a plant-derived compound—on the WNT/β-catenin pathway in CRC. Two CRC cell lines, COLO205 and DLD1, were treated with cryptolepine or XAV 939 (a WNT inhibitor) in the presence or absence of WNT3a (a WNT activator). Using a tetrazolium-based assay, cryptolepine was found to reduce cell viability in a dose- and time-dependent manner and was a more potent inhibitor of viability than XAV 939. RT-qPCR analyses showed that cryptolepine reverses WNT3a-induced expression of β-catenin, c-MYC, and WISP1, suggesting that cryptolepine inhibits WNT3a-mediated activation of WNT/β-catenin signaling. Cryptolepine also repressed WNT3a-induced OCT4 and CD133 expression and suppressed colony formation of the cells, indicating that cryptolepine inhibits the stemness of CRC cells. Additionally, cryptolepine inhibited WNT3a-induced epithelial-to-mesenchymal transition by reducing the expression of SNAI1 and TWIST1 genes. In a wound healing assay, cryptolepine was found to suppress cell migration under unstimulated and WNT3a-stimulated conditions. Moreover, cryptolepine downregulated WNT3a-induced expression of MMP2 and MMP9 genes, which are involved in cancer cell invasion. Altogether, cryptolepine suppresses CRC cell proliferation, stemness, and metastatic properties by inhibiting WNT3a-mediated activation of the WNT/β-catenin signaling pathway. These findings provide a rationale for considering cryptolepine as a potential WNT inhibitor in CRC.

Funder

World Bank African Centres of Excellence

DELTAS Africa

Wellcome Trust

UK Foreign

Commonwealth & Development Office

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

Reference61 articles.

1. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;Sung;CA Cancer J. Clin.,2021

2. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors;Rawla;Prz. Gastroenterol.,2019

3. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy;Nguyen;Oncol. Lett.,2018

4. The World Cancer Research Fund/American Institute for Cancer Research Third Expert Report on Diet, Nutrition, Physical Activity, and Cancer: Impact and Future Directions;Clinton;J. Nutr.,2020

5. Cancer stem cells in colorectal cancer: A review;Munro;J. Clin. Pathol.,2018

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3