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

Title
Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies
Type
Article in International Scientific Journal
Year
2024
Authors
Almeida, CF
(Author)
Other
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Valente, MJ
(Author)
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Georgina Correia da Silva
(Author)
FFUP
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Vinggaard, AM
(Author)
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Emilia Sousa
(Author)
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Teixeira, N
(Author)
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Amaral, C
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Journal
Title: PharmaceuticalsImported from Authenticus Search for Journal Publications
Vol. 17
Final page: 1245
ISSN: 1424-8247
Publisher: MDPI
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Publicação em ISI Web of Knowledge ISI Web of Knowledge - 0 Citations
Publicação em Scopus Scopus - 0 Citations
Other information
Authenticus ID: P-017-4EN
Abstract (EN): 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 Delta 9-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 ER alpha 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.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 31
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