{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:35:19Z","timestamp":1772217319069,"version":"3.50.1"},"reference-count":130,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T00:00:00Z","timestamp":1726876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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 \u03949-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been evaluated in different cancers, including breast. However, Cannabis\u00a0sativa 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\u03b1 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.<\/jats:p>","DOI":"10.3390\/ph17091245","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T03:36:38Z","timestamp":1727062598000},"page":"1245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies"],"prefix":"10.3390","volume":"17","author":[{"given":"Cristina Ferreira","family":"Almeida","sequence":"first","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-2143","authenticated-orcid":false,"given":"Andreia","family":"Palmeira","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, Av. General Norton de Matos S\/N, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-2426","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Valente","sequence":"additional","affiliation":[{"name":"National Food Institute, Technical University of Denmark, 2800 Kongens Lyngby, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-9018","authenticated-orcid":false,"given":"Georgina","family":"Correia-da-Silva","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6822-3572","authenticated-orcid":false,"given":"Anne Marie","family":"Vinggaard","sequence":"additional","affiliation":[{"name":"National Food Institute, Technical University of Denmark, 2800 Kongens Lyngby, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Maria Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, Av. General Norton de Matos S\/N, 4450-208 Matosinhos, Portugal"}]},{"given":"Nat\u00e9rcia","family":"Teixeira","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"}]},{"given":"Cristina","family":"Amaral","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, n\u00b0 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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