Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2023; 15(5): 810-827
Published online May 15, 2023. doi: 10.4251/wjgo.v15.i5.810
BZD9L1 benzimidazole analogue hampers colorectal tumor progression by impeding angiogenesis
Chern Ein Oon, Ayappa V Subramaniam, Lik Yang Ooi, Ashwaq Hamid Salem Yehya, Yeuan Ting Lee, Gurjeet Kaur, Sreenivasan Sasidharan, Beiying Qiu, Xiaomeng Wang
Chern Ein Oon, Ayappa V Subramaniam, Lik Yang Ooi, Yeuan Ting Lee, Gurjeet Kaur, Sreenivasan Sasidharan, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang 11800, Malaysia
Ashwaq Hamid Salem Yehya, Cancer Research, Eman Biodiscoveries, Kedah 08000, Malaysia
Ashwaq Hamid Salem Yehya, Vatche and Tamar Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, United States
Beiying Qiu, Xiaomeng Wang, Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore 169857, Singapore
Beiying Qiu, Singapore National Eye Centre, Singapore Eye Research Institute, Singapore 168751, Singapore
Xiaomeng Wang, Singapore National Eye Centre, Singapore Eye Research Institute, Singapore 169857, Singapore
Author contributions: Oon CE and Subramaniam AV remain to have equal contributions as co-first authors; Oon CE, Subramaniam AV, Ooi LY, and Qiu B carried out the experiments; Lee YT synthesized the BZD9L1 compound; Oon CE drafted and reviewed the manuscript; Subramaniam AV and Ooi LY provided scientific input for “Discussion”; Oon CE, Subramaniam AV, Ooi LY, Qiu B, and Kaur G analyzed the data; Sasidharan S provided scientific input for in vivo study; Wang X derived the ex vivo angiogenesis models; Oon CE conceived and designed the experiments, and supervised the project; and all the authors have read and approved the final manuscript.
Supported by the Ministry of Higher Education Malaysia for the Fundamental Research Grant Scheme, No. FRGS/1/2021/SKK06/USM/02/7.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the National University of Singapore Institutional Animal Care and Use Committee guidelines (approval No. 2020/SHS/1597) and Universiti Sains Malaysia Animal Ethical Committee [approval No. USM/IACUC/2017/(105)(872)].
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Chern Ein Oon, DPhil, PhD, Associate Professor, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor, Penang 11800, Malaysia.
Received: January 3, 2023
Peer-review started: January 3, 2023
First decision: February 13, 2023
Revised: February 17, 2023
Accepted: April 21, 2023
Article in press: April 21, 2023
Published online: May 15, 2023
Core Tip

Core Tip: BZD9L1 hampered EA.hy926 endothelial cell functions through cell cycle arrest and induction of apoptosis. BZD9L1 also reduced the cell adhesion, sirtuin 1 (SIRT1) and SIRT2 gene expression in endothelial cells (EC) compared to the negative control. The compound down-regulated angiogenin, basic fibroblast growth factor, platelet-derived growth factor, and placental growth factor proteins in EC and impeded HCT116 colorectal cancer (CRC) invasion compared to the negative control group. BZD9L1 negatively impacted choroidal sprouting and CRC tumor angiogenesis in vivo compared to the vehicle control group. BZD9L1 reduced tumor necrosis, Ki-67 proliferation marker, hSIRT1, hSIRT2, murine cluster of differentiation 31 (mCD31), mCD34 and murine SIRT2 (mSIRT2) gene expression compared to vehicle control. Findings from this study may provide insights for the BZD9L1 benzimidazole analogue to be further explored as a potential anti-angiogenic agent in CRC.