Associação Portuguesa de Investigação em Cancro
Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies
Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies
Authors and Affiliations:
Cristina Ferreira Almeida1,2, Andreia Palmeira3,4, Maria João Valente5, Georgina Correia-da-Silva1,2, Anne Marie Vinggaard5, Maria Emília Sousa3,4, Natércia Teixeira1,2, Cristina Amaral1,2
1 UCIBIO, 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, Porto, Portugal
4 CIIMAR – Interdisciplinary Centre of Marine and Environmental Research, Matosinhos, Portugal 5 National Food Institute, Technical University of Denmark, 2800 Kongens Lyngby, Denmark
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. 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). 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. 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.
Pharmaceuticals
