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Review

Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies

by
Edilene S. A. Melo
1,
Estefani A. Asevedo
1,
Joaquim Maurício Duarte-Almeida
2,
Fahrul Nurkolis
3,
Rony Abdi Syahputra
4,
Moon Nyeo Park
5,
Bonglee Kim
5,
Renê Oliveira do Couto
6 and
Rosy Iara Maciel de A. Ribeiro
1,*
1
Experimental Pathology Laboratory, Dona Lindu Central-West Campus (CCO), Federal University of São João del-Rei (UFSJ), Sebastião Gonçalves Coelho 400, Chanadour, Divinopolis 35501-296, MG, Brazil
2
Plant Cell Culture Laboratory, Dona Lindu Central-West Campus (CCO), Federal University of São João del-Rei, Sebastião Gonçalves Coelho 400, Chanadour, Divinopolis 35501-296, MG, Brazil
3
Department of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta 55281, Indonesia
4
Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Indonesia
5
Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
6
Pharmaceutical Development Laboratory, Dona Lindu Central-West Campus (CCO), Federal University of São João del-Rei, Sebastião Gonçalves Coelho 400, Chanadour, Divinopolis 35501-296, MG, Brazil
*
Author to whom correspondence should be addressed.
Plants 2025, 14(4), 585; https://doi.org/10.3390/plants14040585
Submission received: 24 December 2024 / Revised: 9 February 2025 / Accepted: 11 February 2025 / Published: 14 February 2025
(This article belongs to the Special Issue Bioprospecting the Efficacy and Safety of Natural Products from Plants)
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Abstract

Commonly known as marijuana or hemp, Cannabis sativa L. (Cannabaceae), contains numerous active compounds, particularly cannabinoids, which have been extensively studied for their biological activities. Among these, cannabidiol (CBD) stands out for its therapeutic potential, especially given its non-psychotropic effects. This review evaluates the antitumor properties of CBD, highlighting its various mechanisms of action, including the induction of apoptosis, autophagy, and necrosis. By synthesizing findings from in vitro studies on the cell death mechanisms and signaling pathways activated by CBD in various human tumor cell lines, this literature review emphasizes the therapeutic promise of this natural antineoplastic agent. We conducted a comprehensive search of articles in PubMed, Scopus, Springer, Medline, Lilacs, and Scielo databases from 1984 to February 2022. Of the forty-three articles included, the majority (68.18%) reported that CBD activates apoptosis, while 18.18% observed simultaneous apoptosis and autophagy, 9.09% focused on autophagy alone, and 4.54% indicated necrosis. The antitumor effects of CBD appear to be mediated by transient receptor potential cation channels (TRPVs) in endometrial cancer, glioma, bladder cancer, and myeloma, with TRPV1, TRPV2, and TRPV4 playing key roles in activating apoptosis. This knowledge paves the way for innovative therapeutic strategies that may enhance cancer treatment outcomes while minimizing the toxicity and side effects associated with conventional therapies.
Keywords: cannabidiol; antineoplastic agents; transient receptor potential channels; preclinical drug evaluation cannabidiol; antineoplastic agents; transient receptor potential channels; preclinical drug evaluation

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MDPI and ACS Style

Melo, E.S.A.; Asevedo, E.A.; Duarte-Almeida, J.M.; Nurkolis, F.; Syahputra, R.A.; Park, M.N.; Kim, B.; Couto, R.O.d.; Ribeiro, R.I.M.d.A. Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies. Plants 2025, 14, 585. https://doi.org/10.3390/plants14040585

AMA Style

Melo ESA, Asevedo EA, Duarte-Almeida JM, Nurkolis F, Syahputra RA, Park MN, Kim B, Couto ROd, Ribeiro RIMdA. Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies. Plants. 2025; 14(4):585. https://doi.org/10.3390/plants14040585

Chicago/Turabian Style

Melo, Edilene S. A., Estefani A. Asevedo, Joaquim Maurício Duarte-Almeida, Fahrul Nurkolis, Rony Abdi Syahputra, Moon Nyeo Park, Bonglee Kim, Renê Oliveira do Couto, and Rosy Iara Maciel de A. Ribeiro. 2025. "Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies" Plants 14, no. 4: 585. https://doi.org/10.3390/plants14040585

APA Style

Melo, E. S. A., Asevedo, E. A., Duarte-Almeida, J. M., Nurkolis, F., Syahputra, R. A., Park, M. N., Kim, B., Couto, R. O. d., & Ribeiro, R. I. M. d. A. (2025). Mechanisms of Cell Death Induced by Cannabidiol Against Tumor Cells: A Review of Preclinical Studies. Plants, 14(4), 585. https://doi.org/10.3390/plants14040585

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