Unveiling the mechanism of action behind the anti-cancer properties of cannabinoids in ER+ breast cancer cells: Impact on aromatase and steroid receptors

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Unveiling the mechanism of action behind the anti-cancer properties of cannabinoids in ER+ breast cancer cells: Impact on aromatase and steroid receptors

Sexta, 09.04.2021

Autores e Afiliações:

Cristina Amaral, Fabien Marc Trouille, Cristina Ferreira Almeida, Georgina Correia-da-Silva, Natércia Teixeira

UCIBIO.REQUIMTE, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto

 

Abstract:

Breast cancer is currently the leading cause of cancer-related death in women worldwide. Despite the therapeutic efficacy of the current treatments used in clinic, most of the drugs cause several side effects that limit their effectiveness and that is why it is urgent to discover new anti-cancer drugs for the treatment of this cancer. In the last years and since it was approved by law in several countries, the Cannabis Sativa plant and cannabinoids have gained attention in the clinical setting, in particular in oncology. In fact, due to their palliative properties in pain and in relieving chemotherapy side effects, some cannabinoid-based drugs have already been approved or are underway in clinical trials. In addition, anti-tumor properties in several cancer cells have been reported in literature, however, there is no evidence of cannabinoids impact on estrogen receptor positive (ER +) breast cancer. With this work, our group has elucidated, for the first time, the molecular mechanisms underlying the anti-cancer properties of the endocannabinoid anandamide (AEA) and of the phytocannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), in ER+ breast cancer cells. We showed that these cannabinoids prevent growth and induce death of cancer cells, not only by blocking the activity and reducing the expression of aromatase and ERα, but also by up-regulating ERβ levels. As aromatase and both ERs are key therapeutic targets for the treatment of this type of tumors, this work indicates that these cannabinoids can be considered as potential and attractive therapeutic molecules for this type of cancer, being CBD the most promising cannabinoid. Moreover, this work provided relevant information that strengthens the potential clinical application of cannabinoids and cannabinoid-based drugs in this clinical setting. However, subsequent studies are being developed by our research group to further detail this potential application.

 

Revista: The Journal of Steroid Biochemistry and Molecular Biology

 

Linkhttps://www.sciencedirect.com/science/article/abs/pii/S0960076021000698?dgcid=author