Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights

Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and current treatments have significant side effects. Cannabidiol (CBD), a compound derived from <i>Cannabis sativa</i>, has demonstrated promising anticancer properties. However, further investigation is...

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Main Authors: Juan Manuel Guzmán-Flores, Fernando Martínez-Esquivias, Antistio Alviz-Amador, Guadalupe Thonanzyn Avilés-Rodríguez, Michel Fabricio García-Azuela
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Scientia Pharmaceutica
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Online Access:https://www.mdpi.com/2218-0532/93/1/12
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author Juan Manuel Guzmán-Flores
Fernando Martínez-Esquivias
Antistio Alviz-Amador
Guadalupe Thonanzyn Avilés-Rodríguez
Michel Fabricio García-Azuela
author_facet Juan Manuel Guzmán-Flores
Fernando Martínez-Esquivias
Antistio Alviz-Amador
Guadalupe Thonanzyn Avilés-Rodríguez
Michel Fabricio García-Azuela
author_sort Juan Manuel Guzmán-Flores
collection DOAJ
description Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and current treatments have significant side effects. Cannabidiol (CBD), a compound derived from <i>Cannabis sativa</i>, has demonstrated promising anticancer properties. However, further investigation is required to elucidate its underlying molecular mechanisms. Methods: Network pharmacology and molecular docking analysis approaches were utilized. Molecular targets of CBD and CRC-associated genes were identified using the Swiss Target Prediction, Malacards, and DisGeNet databases. Protein–protein interactions were analyzed using the STRING and Cytoscape. Ontology enrichment was conducted using ShinyGO, and gene expression and immune infiltration were evaluated with UALCAN and TISIDB. Results: We found 95 common genes between CRC and CBD targets. Six major genes (ANXA5, IGF1R, JAK2, MAPK8, MDM2, and PARP1) were particularly interesting due to their high connectivity and role in relevant metabolic pathways. The results of the molecular docking analysis indicated that CBD interacts favorably with these genes, modulating critical pathways such as RAS/MAPK and PI3K-AKT/FoxO, which are involved in cell proliferation, apoptosis, and cell cycle regulation. ANXA5 and JAK2 were identified as particularly relevant, as they correlated significantly with immune cell infiltration, suggesting a role in the immunoregulation of the tumor microenvironment. Conclusions: CBD has the potential to modulate key molecular processes in CRC through specific pathways and core genes, presenting itself as a possible complementary therapy to improve efficacy and reduce the adverse effects of conventional treatments.
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spelling doaj-art-f7d07d06844444569f3fa01bc2dd1e3f2025-08-20T01:49:03ZengMDPI AGScientia Pharmaceutica0036-87092218-05322025-02-019311210.3390/scipharm93010012Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking InsightsJuan Manuel Guzmán-Flores0Fernando Martínez-Esquivias1Antistio Alviz-Amador2Guadalupe Thonanzyn Avilés-Rodríguez3Michel Fabricio García-Azuela4Departamento de Ciencias de la Salud, Centro Universitario de Los Altos, Universidad de Guadalajara, Tepatitlán de Morelos C.P. 47620, Jalisco, MexicoDepartamento de Ciencias de la Salud, Centro Universitario de Los Altos, Universidad de Guadalajara, Tepatitlán de Morelos C.P. 47620, Jalisco, MexicoPharmacology and Therapeutic Group, Faculty of Pharmaceutical Sciences, University of Cartagena, Cartagena 130014, ColombiaLicenciatura en Biomedicina, Facultad de Biología, Universidad Autónoma de Sinaloa, Culiacán C.P. 80013, Sinaloa, MexicoLicenciatura en Químico Farmacéutico Biólogo, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara C.P. 44430, Jalisco, MexicoBackground: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and current treatments have significant side effects. Cannabidiol (CBD), a compound derived from <i>Cannabis sativa</i>, has demonstrated promising anticancer properties. However, further investigation is required to elucidate its underlying molecular mechanisms. Methods: Network pharmacology and molecular docking analysis approaches were utilized. Molecular targets of CBD and CRC-associated genes were identified using the Swiss Target Prediction, Malacards, and DisGeNet databases. Protein–protein interactions were analyzed using the STRING and Cytoscape. Ontology enrichment was conducted using ShinyGO, and gene expression and immune infiltration were evaluated with UALCAN and TISIDB. Results: We found 95 common genes between CRC and CBD targets. Six major genes (ANXA5, IGF1R, JAK2, MAPK8, MDM2, and PARP1) were particularly interesting due to their high connectivity and role in relevant metabolic pathways. The results of the molecular docking analysis indicated that CBD interacts favorably with these genes, modulating critical pathways such as RAS/MAPK and PI3K-AKT/FoxO, which are involved in cell proliferation, apoptosis, and cell cycle regulation. ANXA5 and JAK2 were identified as particularly relevant, as they correlated significantly with immune cell infiltration, suggesting a role in the immunoregulation of the tumor microenvironment. Conclusions: CBD has the potential to modulate key molecular processes in CRC through specific pathways and core genes, presenting itself as a possible complementary therapy to improve efficacy and reduce the adverse effects of conventional treatments.https://www.mdpi.com/2218-0532/93/1/12network pharmacologymolecular dockingcannabidiolcolorectal cancerimmunity
spellingShingle Juan Manuel Guzmán-Flores
Fernando Martínez-Esquivias
Antistio Alviz-Amador
Guadalupe Thonanzyn Avilés-Rodríguez
Michel Fabricio García-Azuela
Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights
Scientia Pharmaceutica
network pharmacology
molecular docking
cannabidiol
colorectal cancer
immunity
title Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights
title_full Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights
title_fullStr Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights
title_full_unstemmed Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights
title_short Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights
title_sort exploring cannabidiol s therapeutic role in colorectal cancer network pharmacology and molecular docking insights
topic network pharmacology
molecular docking
cannabidiol
colorectal cancer
immunity
url https://www.mdpi.com/2218-0532/93/1/12
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