Glucose starvation greatly enhances antiproliferative and antiestrogenic potency of oligomycin A in MCF-7 breast cancer cells.
Biochimie
; 186: 51-58, 2021 Jul.
Article
in En
| MEDLINE
| ID: mdl-33872751
ABSTRACT
Energy imbalance is one of the key properties of tumour cells, which in certain cases supports fast cancer progression and resistance to therapy. The simultaneous blocking of glycolytic processes and oxidative phosphorylation pathways seems to be a promising strategy for antitumor therapies. The study aimed to evaluate the effect of glucose starvation on the antiproliferative and antiestrogenic potency of oligomycin A against hormone-dependent breast cancer cells. Cell viability was assessed by the MTT test. Estrogen receptor alpha (ERα) activity was evaluated by reporter assay. mTOR, AMPK, Akt, and S6 kinase expression was assessed by immunoblotting. Glucose starvation caused multiple increases in the antiproliferative potency of oligomycin A in the hormone-dependent breast cancer MCF-7 cells, while its effect on the sensitivity of the second hormone-dependent cancer cell line, named T47D, was weak and limited. Glycolytic inhibitors, 3-bromopyruvate and 2-deoxyglucose, greatly enhanced the antiproliferative potency of oligomycin A in MCF-7 cells. Glucose starvation leads to remarkable activation of Akt in MCF-7 cells, whereas oligomycin A enhances its effect. The mTOR, S6 kinase, and AMPK signalling pathways are significantly modulated by oligomycin A under glucose starvation. Oligomycin A demonstrates more pronounced antiestrogenic effects under glucose starvation. Thus, glucose starvation and pharmacological inhibition of glycolysis are of interest for revealing the antitumor potential of macrolide oligomycin A against hormone-dependent breast cancers.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligomycins
/
Breast Neoplasms
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Estrogen Receptor Modulators
/
Cell Proliferation
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Glucose
Limits:
Female
/
Humans
Language:
En
Journal:
Biochimie
Year:
2021
Document type:
Article