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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Reticuline and Coclaurine Exhibit Vitamin D Receptor-Dependent Anticancer and Pro-Apoptotic Activities in the Colorectal Cancer Cell Line HCT116

by
Hind A. Alghamdi
1,2,3,
Sahar S. Alghamdi
4,5,
Maryam Hassan Al-Zahrani
1,
Thadeo Trivilegio
5,
Sara Bahattab
2,
Rehab AlRoshody
2,
Yazeid Alhaidan
6,
Rana A. Alghamdi
7,8 and
Sabine Matou-Nasri
2,9,*
1
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
2
Blood and Cancer Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh 11481, Saudi Arabia
3
Chemistry Department, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
4
Pharmaceutical Sciences Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard-Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia
5
Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh 11481, Saudi Arabia
6
Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh 11481, Saudi Arabia
7
Department of Chemistry, Science and Arts College, King Abdulaziz University, Rabigh 25732, Saudi Arabia
8
Regenerative Medicine Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia
9
Biosciences Department, Faculty of the School of Systems Biology, George Mason University, Manassas, VA 20110, USA
*
Author to whom correspondence should be addressed.
Curr. Issues Mol. Biol. 2025, 47(10), 810; https://doi.org/10.3390/cimb47100810
Submission received: 1 September 2025 / Revised: 24 September 2025 / Accepted: 29 September 2025 / Published: 1 October 2025
(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)
Review Reports Versions Notes

Abstract

Alkaloids have garnered significant interest as potential anticancer agents. Vitamin D receptor (VDR) plays a role in preventing the progression of colorectal cancer (CRC) and may be a crucial mediator of the anticancer effects produced by certain alkaloids. The search for novel anticancer drugs that induce VDR expression and act through the VDR could improve the clinical outcomes of CRC patients. The anticancer and pro-apoptotic effects of coclaurine and reticuline were investigated using CRISPR/Cas9-edited VDR/knockout (KO) and wild-type (WT) CRC HCT116 cell lines. Western blotting, RT-qPCR, confocal microscopy, cell viability, scratch assays, and flow cytometry were employed to assess VDR expression and cellular localization, cell growth, wound-healing, cytotoxicity, apoptotic status, cell cycle progression, and VDR-mediated gene expression. Coclaurine and reticuline dose-dependently inhibited HCT116-WT cell viability, decreased wound-healing, and increased VDR nuclear localization and gene expression while downregulating the oncogenic genes SNAIL1 and SNAIL2. Both alkaloids induced late apoptosis in HCT116-WT cells, increased the cleavage of PARP and caspase-3, and upregulated Bax and TP53 while decreasing BCL-2. Both alkaloids caused HCT116-WT cell growth arrest in the S-phase, which is associated with cyclin A1 overexpression. Coclaurine and reticuline lost their anticancer effects in HCT116-VDR/KO cells. Docking studies revealed that both alkaloids occupied the VDR’s active site. These findings demonstrate that coclaurine and reticuline exert anti-CRC and pro-apoptotic activities via the VDR, suggesting them as natural therapeutic candidates. The use of in vivo CRC models is needed to validate the anticancer activities of coclaurine and reticuline.
Keywords: colorectal cancer; vitamin D receptor; vitamin D3; coclaurine; reticuline; anticancer; apoptosis; molecular docking colorectal cancer; vitamin D receptor; vitamin D3; coclaurine; reticuline; anticancer; apoptosis; molecular docking

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MDPI and ACS Style

Alghamdi, H.A.; Alghamdi, S.S.; Al-Zahrani, M.H.; Trivilegio, T.; Bahattab, S.; AlRoshody, R.; Alhaidan, Y.; Alghamdi, R.A.; Matou-Nasri, S. Reticuline and Coclaurine Exhibit Vitamin D Receptor-Dependent Anticancer and Pro-Apoptotic Activities in the Colorectal Cancer Cell Line HCT116. Curr. Issues Mol. Biol. 2025, 47, 810. https://doi.org/10.3390/cimb47100810

AMA Style

Alghamdi HA, Alghamdi SS, Al-Zahrani MH, Trivilegio T, Bahattab S, AlRoshody R, Alhaidan Y, Alghamdi RA, Matou-Nasri S. Reticuline and Coclaurine Exhibit Vitamin D Receptor-Dependent Anticancer and Pro-Apoptotic Activities in the Colorectal Cancer Cell Line HCT116. Current Issues in Molecular Biology. 2025; 47(10):810. https://doi.org/10.3390/cimb47100810

Chicago/Turabian Style

Alghamdi, Hind A., Sahar S. Alghamdi, Maryam Hassan Al-Zahrani, Thadeo Trivilegio, Sara Bahattab, Rehab AlRoshody, Yazeid Alhaidan, Rana A. Alghamdi, and Sabine Matou-Nasri. 2025. "Reticuline and Coclaurine Exhibit Vitamin D Receptor-Dependent Anticancer and Pro-Apoptotic Activities in the Colorectal Cancer Cell Line HCT116" Current Issues in Molecular Biology 47, no. 10: 810. https://doi.org/10.3390/cimb47100810

APA Style

Alghamdi, H. A., Alghamdi, S. S., Al-Zahrani, M. H., Trivilegio, T., Bahattab, S., AlRoshody, R., Alhaidan, Y., Alghamdi, R. A., & Matou-Nasri, S. (2025). Reticuline and Coclaurine Exhibit Vitamin D Receptor-Dependent Anticancer and Pro-Apoptotic Activities in the Colorectal Cancer Cell Line HCT116. Current Issues in Molecular Biology, 47(10), 810. https://doi.org/10.3390/cimb47100810

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