Antiproliferative effects of 13α/ß-steroids on triple-negative MDA-MB-231 breast cancer cells: unraveling intracellular signaling without ERα
Braz. J. Pharm. Sci. (Online)
; 59: e22540, 2023. tab, graf
Article
in English
| LILACS
| ID: biblio-1439522
Responsible library:
BR40.1
Localization: BR40.1
ABSTRACT
Abstract This study aimed to investigate the activities of novel 20(R)-3,20-dihydroxy-19-norpregn-1,3,5(10)-trienes (kuz7 and kuz8b) of natural 13ß- and epimeric 13α-series against triple-negative MDA-MB-231 breast cancer cells. High antiproliferative activity of synthesized compounds kuz8b and kuz7 against MDA-MB-231 triple-negative cancer cells was revealed. The steroid kuz7 of natural 13ß-configuration was more active against MDA-MB-231 cells than the 13α-steroid kuz8b. Cell cycle analysis revealed common patterns for the action of both tested compounds. The number of cells in the subG1 phase increased in a dose-dependent manner, indicating induction of apoptosis, which was also verified by PARP cleavage. In contrast, the number of cells in the G0/G1 phase decreases with increasing compound concentration. Steroid kuz7 at micromolar concentrations reduced the expression of GLUT1, a glucose transporter. High efficacy of the combination of kuz7 with biguanide metformin was shown, and synergistic effects on MDA-MB-231 cell growth and expression of the anti-apoptotic protein Bcl-2 were revealed. According to the obtained results, including the high activity of kuz7 against triple-negative cancer cells, the detected induction of apoptosis, and the decrease in GLUT1 expression, 13ß-steroid kuz7 is of interest for further preclinical studies both alone and in combination with the metabolic drug metformin
Full text:
Available
Collection:
International databases
Health context:
SDG3 - Target 3.4 Reduce premature mortality due to noncommunicable diseases
Health problem:
Breast Cancer
Database:
LILACS
Main subject:
Steroids
/
Breast Neoplasms
/
Glucose Transporter Type 1
Language:
English
Journal:
Braz. J. Pharm. Sci. (Online)
Journal subject:
Farmacologia
/
Teraputica
/
Toxicologia
Year:
2023
Document type:
Article
Affiliation country:
RUSSIA
Institution/Affiliation country:
N.N. Blokhin National Medical Research Center of Oncology/RU
/
Russian Academy of Sciences/RU