In Vitro Effects of Combining Genistein with Aromatase Inhibitors: Concerns Regarding Its Consumption during Breast Cancer Treatment

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 13; p. 4893
• Main Authors: Bezerra, Patrícia H A, Amaral, Cristina, Almeida, Cristina F, Correia-da-Silva, Georgina, Torqueti, Maria Regina, Teixeira, Natércia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.06.2023; MDPI
• Subjects: Anastrozole; Antineoplastic Agents - therapeutic use; Apoptosis; Aromatase; Aromatase Inhibitors - pharmacology; Aromatase Inhibitors - therapeutic use; Autophagy; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cancer therapies; Cell cycle; Cell growth; Cell proliferation; Enzymes; Estrogen receptors; Estrogens; Exemestane; Female; Genistein; Genistein - pharmacology; Genistein - therapeutic use; Humans; Inhibitors; Kinases; Letrozole; luminal A; Medical prognosis; Nitriles - therapeutic use; Phytoestrogens; Senescence; Soybeans; Tumors; androgen receptor; aromatase; genistein; Anastrozole; estrogen receptor; breast cancer; Exemestane; anticancer drugs; luminal A; Letrozole
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28134893

The third-generation of aromatase inhibitors (AIs)-Exemestane (Exe), Letrozole (Let), and Anastrozole (Ana)-is the main therapeutic approach applied for estrogen receptor-positive (ER+) breast cancer (BC), the most common neoplasm in women worldwide. Despite their success, the development of resistance limits their efficacy. Genistein (G), a phytoestrogen present in soybean, has promising anticancer properties in ER+ BC cells, even when combined with anticancer drugs. Thus, the potential beneficial effects of combining G with AIs were investigated in sensitive (MCF7-aro) and resistant (LTEDaro) BC cells. The effects on cell proliferation and expression of aromatase, ERα/ERβ, and AR receptors were evaluated. Unlike the combination of G with Ana or Let, which negatively affects the Ais' therapeutic efficacy, G enhanced the anticancer properties of the steroidal AI Exe, increasing the antiproliferative effect and apoptosis relative to Exe. The hormone targets studied were not affected by this combination when compared with Exe. This is the first study that highlights the potential benefit of G as an adjuvant therapy with Exe, emphasizing, however, that soy derivatives widely used in the diet or applied as auxiliary medicines may increase the risk of adverse interactions with nonsteroidal AIs used in therapy.