Steroidal aromatase inhibitors inhibit growth of hormone-dependent breast cancer cells by inducing cell cycle arrest and apoptosis

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Cristina Amaral (Author) Other; Carla Varela (Author) Other; Margarida Borges (Author) FFUP; Elisiario Tavares da Silva (Author) Other; Fernanda M F Roleira (Author) Other; Georgina Correia da Silva (Author) FFUP; Natercia Teixeira (Author) FFUP

Journal

Title: APOPTOSIS

Vol. 18

ISSN: 13608185

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 18 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-006-6BF

Abstract (EN): Different hormonal therapies are used for estrogen receptor positive (ER+) breast cancers, being the third-generation of aromatase inhibitors (AIs), an effective alternative to the classical tamoxifen. AIs inhibit the enzyme aromatase, which is responsible for catalyzing the conversion of androgens to estrogens. In this study, it was evaluated the effects of several steroidal AIs, namely 3 beta-hydroxyandrost-4-en-17-one (1), androst-4-en-17-one (12), 4 alpha,5 alpha-epoxyandrostan-17-one (13a) and 5 alpha-androst-2-en-17-one (16), on cell proliferation, cell cycle progression and cell death in an ER+ aromatase-overexpressing human breast cancer cell line (MCF-7aro). All AIs induced a decrease in cell proliferation and these anti-proliferative effects were due to a disruption in cell cycle progression and cell death, by apoptosis. AIs 1 and 16 caused cell cycle arrest in G(0)/G(1), while AIs 12 and 13a induced an arrest in G(2)/M. Moreover, it was observed that these AIs induced apoptosis by different pathways, since AIs 1, 12 and 13a activated the apoptotic mitochondrial pathway, while AI 16 induced apoptosis through activation of caspase-8. These results are important for the elucidation of the cellular effects of steroidal AIs on breast cancer cells and will also highlight the importance of AIs as inducers of apoptosis in hormone-dependent breast cancers.

Language: English

Type (Professor's evaluation): Scientific