Go to:
Logótipo
Comuta visibilidade da coluna esquerda
Você está em: Start > Publications > View > Effects of new C6-substituted steroidal aromatase inhibitors in hormone-sensitive breast cancer cells: Cell death mechanisms and modulation of estrogen and androgen receptors
Publication

Publications

Effects of new C6-substituted steroidal aromatase inhibitors in hormone-sensitive breast cancer cells: Cell death mechanisms and modulation of estrogen and androgen receptors

Title
Effects of new C6-substituted steroidal aromatase inhibitors in hormone-sensitive breast cancer cells: Cell death mechanisms and modulation of estrogen and androgen receptors
Type
Article in International Scientific Journal
Year
2019
Authors
Augusto, TV
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Amaral, C
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Varela, CL
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Bernardo, F
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
da Silva, ET
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Roleira, FFM
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Costa, S
(Author)
Other
The person does not belong to the institution. The person does not belong to the institution. The person does not belong to the institution. Without AUTHENTICUS Without ORCID
Georgina Correia da Silva
(Author)
FFUP
View Personal Page You do not have permissions to view the institutional email. Search for Participant Publications View Authenticus page Without ORCID
Journal
Vol. 195
ISSN: 0960-0760
Publisher: Elsevier
Other information
Authenticus ID: P-00R-4CF
Abstract (EN): Estrogen receptor-positive (ER+) breast cancers require estrogens for their growth. Aromatase inhibitors (AIs) are considered the first-line therapy for this type of tumours. Despite the well-established clinical benefit of this therapy, the search for novel potent AIs that present higher efficacy and fewer side effects is still demanded. Thus, taking into account the known interactions of the natural substrate, androstenedione, within the aromatace active-site, a range of new steroidal compounds have been designed, synthesized and studied by our group. In this work, it was evaluated in MCF-7aro, an ER+ breast cancer cell line that overexpress aromatase, the anti-aromatase efficacy and the biological effects of eight new AIs: 6 alpha-methyl-5 alpha-androst-3-en-17-one (1a), 6 alpha-methyl-3 alpha,4 alpha-epoxy-5 alpha-androstan-17-one (3a), 6 alpha-methylandrost-4-ene-3,17-dione (9), 6 alpha-allylandrosta-1,4diene-3,17-dione (13), 6 alpha-allylandrost-4-ene-3,17-dione (15), 6 alpha-allylandrost-4-en-17-one (17), 60-hydroxyandrost-4-ene-3,17-dione (19) and 6 alpha-hydroxyandrost-4-ene-3,17-dione (20). Their anti-cancer properties were elucidated, as well as, the dependence of their mechanism of action on aromatase inhibition and/or on steroid receptors modulation, such as estrogen and androgen receptors, which are key targets for this type of cancer. Results demonstrate that the studied AIs present high anti-aromatase activity, disrupt MCF-7aro cell cycle progression and induce apoptosis, through the mitochondrial pathway. Compounds 1a, 3a, 9, 13, 15 and 17 exhibited an aromatase-dependent effect on cells and, interestingly, steroids 9 and 13 displayed the ability to decrease aromatase protein levels without affecting CYP19A1 mRNA levels. Furthermore, the effects of compounds 1a, 3a and 15 were dependent on ER and on AR modulation, whereas compounds 9 and 19 were only dependent on AR modulation. From a clinical point of view, these actions can be considered as a therapeutic advantage for this type of tumours. Thus, new promising Ms that impair ER+ breast cancer cell growth, by acting on aromatase, and even, on ER and AR were discovered. Furthermore, new insights on the most favourable structural modifications in the steroidal core structure were provided, helping to a more rational drug design of new and potent AIs.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 9
Documents
We could not find any documents associated to the publication.
Related Publications

Of the same journal

Unravelling exemestane: From biology to clinical prospects (2016)
Another Publication in an International Scientific Journal
Sobral, AF; Amaral, C; Georgina Correia da Silva; Teixeira, NA
Unveiling the mechanism of action behind the anti-cancer properties of cannabinoids in ER+ breast cancer cells: Impact on aromatase and steroid receptors (2021)
Article in International Scientific Journal
Amaral, C; Trouille, FM; Almeida, CF; Georgina Correia da Silva; Teixeira, N
The endocannabinoid system expression in the female reproductive tract is modulated by estrogen (2017)
Article in International Scientific Journal
Maia, J; Almada, M; Silva, A; Georgina Correia da Silva; Teixeira, NA; Sa, SI; Fonseca, BM
Serum 25-hydroxyvitamin D levels in a healthy population from the North of Portugal (2018)
Article in International Scientific Journal
Bettencourt, A; Boleixa, D; Rei, J; Oliveira, JC; Mendonca, D; costa, pp; da Silva, BM; Marinho, A; da Silva, AM
Role of steroid hormones and prolactin in canine mammary cancer (2005)
Article in International Scientific Journal
Queiroga, FL; Perez Alenza, MD; Silvan, G; Pena, L; Lopes, C; Illera, JC

See all (15)

Recommend this page Top
Copyright 1996-2025 © Faculdade de Direito da Universidade do Porto  I Terms and Conditions  I Acessibility  I Index A-Z
Page created on: 2025-07-24 at 23:07:59 | Privacy Policy | Personal Data Protection Policy | Whistleblowing