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Volume 17
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Article

Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies

by
Cristina Ferreira Almeida
1,2,
Andreia Palmeira
3,4,
Maria João Valente
5,
Georgina Correia-da-Silva
1,2,
Anne Marie Vinggaard
5,
Maria Emília Sousa
3,4,
Natércia Teixeira
1,2 and
Cristina Amaral
1,2,*
1
UCIBIO—Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal
2
Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal
3
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal
4
CIIMAR—Interdisciplinary Centre of Marine and Environmental Research, Av. General Norton de Matos S/N, 4450-208 Matosinhos, Portugal
5
National Food Institute, Technical University of Denmark, 2800 Kongens Lyngby, Denmark
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2024, 17(9), 1245; https://doi.org/10.3390/ph17091245
Submission received: 17 July 2024 / Revised: 4 September 2024 / Accepted: 18 September 2024 / Published: 21 September 2024
(This article belongs to the Special Issue Therapeutic Potential for Cannabinoid and Its Receptor)
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Abstract

Background: Breast cancer therapy has been facing remarkable changes. Classic treatments are now combined with other therapies to improve efficacy and surpass resistance. Indeed, the emergence of resistance demands the development of novel therapeutic approaches. Due to key estrogen signaling, estrogen receptor-positive (ER+) breast cancer treatment has always been focused on aromatase inhibition and ER modulation. Lately, the effects of phytocannabinoids, mainly Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been evaluated in different cancers, including breast. However, Cannabis sativa contains more than 120 phytocannabinoids less researched and understood. Methods: Here, we evaluated, both in silico and in vitro, the ability of 129 phytocannabinoids to modulate important molecular targets in ER+ breast cancer: aromatase, ER, and androgen receptor (AR). Results: In silico results suggested that some cannabinoids may inhibit aromatase and act as ERα antagonists. Nine selected cannabinoids showed, in vitro, potential to act either as ER antagonists with inverse agonist properties, or as ER agonists. Moreover, these cannabinoids were considered as weak aromatase inhibitors and AR antagonists with inverse agonist action. Conclusions: Overall, we present, for the first time, a comprehensive analysis of the actions of the phytocannabinoids in targets of ER+ breast tumors, pointing out their therapeutic potential in cancer and in other diseases.
Keywords: phytocannabinoids; medicinal cannabis; breast cancer; aromatase; estrogen receptor; androgen receptor phytocannabinoids; medicinal cannabis; breast cancer; aromatase; estrogen receptor; androgen receptor
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MDPI and ACS Style

Almeida, C.F.; Palmeira, A.; Valente, M.J.; Correia-da-Silva, G.; Vinggaard, A.M.; Sousa, M.E.; Teixeira, N.; Amaral, C. Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies. Pharmaceuticals 2024, 17, 1245. https://doi.org/10.3390/ph17091245

AMA Style

Almeida CF, Palmeira A, Valente MJ, Correia-da-Silva G, Vinggaard AM, Sousa ME, Teixeira N, Amaral C. Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies. Pharmaceuticals. 2024; 17(9):1245. https://doi.org/10.3390/ph17091245

Chicago/Turabian Style

Almeida, Cristina Ferreira, Andreia Palmeira, Maria João Valente, Georgina Correia-da-Silva, Anne Marie Vinggaard, Maria Emília Sousa, Natércia Teixeira, and Cristina Amaral. 2024. "Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies" Pharmaceuticals 17, no. 9: 1245. https://doi.org/10.3390/ph17091245

APA Style

Almeida, C. F., Palmeira, A., Valente, M. J., Correia-da-Silva, G., Vinggaard, A. M., Sousa, M. E., Teixeira, N., & Amaral, C. (2024). Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies. Pharmaceuticals, 17(9), 1245. https://doi.org/10.3390/ph17091245

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