Glucose starvation greatly enhances antiproliferative and antiestrogenic potency of oligomycin A in MCF-7 breast cancer cells

Scherbakov, Alexander M.; Sorokin, Danila V.; Omelchuk, Olga A.; Shchekotikhin, Andrey E.; Красильников, М. А.

doi:10.1016/j.biochi.2021.04.003

Cited by 5 publications

(5 citation statements)

References 58 publications

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“…Although there are some recent reports on the effects of oligomycins on cell proliferation, ,, the underlying mechanisms on cell proliferation remain largely unknown. Since the cell cycle is an important biological process regulating cell proliferation, we analyzed the effect of oligomycins on cell cycle by flow cytometry.…”

Section: Results and Discussionmentioning

confidence: 99%

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5

Feng,

Li,

et al. 2024

J. Agric. Food Chem.

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Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)-and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycinproducing strain, Streptomyces sp. FXY-T5. Chemical investigation led to the discovery of five new oligomycins, 24-lumooligomycin B (1), 4-lumooligomycin B (2), 6-lumooligomycin B (3), 40-homooligomycin B (4), and 15-hydroxy-oligomycin B (5), together with seven biosynthetically related known derivatives. Their structures were assigned by MS, NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. The biosynthesis pathway of oligomycins was first proposed based on the analysis of a type I modular polyketide synthase (PKS) system and targeted gene disruption. As expected, the isolated oligomycins showed significant antiagricultural fungal pathogen activity and antiproliferative properties from which the possible structure− activity relationships were first suggested. More importantly, oligomycins induced significant G1-phase cell cycle arrest on cancer cells and significantly attenuated their Cyclin D1 and PCNA expression through a β-catenin signaling pathway.

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Section: Results and Discussionmentioning

confidence: 99%

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5

Feng,

Li,

et al. 2024

J. Agric. Food Chem.

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“…In fact, this temperature dependence of ERα conformational changes, always seen in the case of AP-1 transcriptions, may reflect a two-step mechanism: the first step corresponds to ERα intracellular trafficking, eventually reflected in weak ERE transcriptions, and the second is relevant to the association of this formatted receptor with the AP1 complex to active a TRE with TPA. A physiological/pathological thermodynamic regulation is logically related to energy production changes [60], represented by the temperature dependence of binding affinity. Hence, according to our data, AP-1/ERE antagonism would govern the development of breast cancers according to energy-regulating cycles in which the mitochondria are implicated [61].…”

Section: Discussionmentioning

confidence: 99%

Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy

Leclercq

2024

Endocrines

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The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing substituents in position 11β that might not only contribute to the development of drugs to alleviate this unfortunate issue but that may be also helpful in identifying molecular aspects of resistance to this receptor in order to elaborate other therapeutic approaches. In this regard, AP-1 assisted and ERE-directed ERα transcriptions are demonstrated to be key factors in this area: AP-1 transcriptions are shown to antagonize ERE transcriptions, thereby limiting their tumor-promoting activity. This property results from a conformal change in the receptor, which is induced essentially by estrogenic ligands which, inserted into a cavity of ERα’s ligand-binding pocket, govern this regulatory mechanism. Flexible 11β side-chains favor this insertion, in contrast to their rigid counterparts, which counteract it; these properties give rise to strong estrogenic, SERM or SERD profiles. Suspected extracellular regulatory mechanisms resulting from these ligand-induced transcriptions are elaborated on in the present work in the context of breast cancer development.

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“…Therefore, additional therapeutic approaches are required to improve the clinical outcomes of CDN1 and CDN3, and we screened 2 potential therapeutic drugs for CDN1, including brefeldin A and oligomycin A. Because of its apoptosis-inducing activity in cancer cells, brefeldin A may act as a sensitive drug for CDN1 isoforms[48], and oligomycin A can suppress tumors by inhibiting the proliferation of tumor cells [49]. No sensitive drugs were screened in CDN3, but CDN3 showed elevated lipid metabolism and glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk of cell death pathways implicates heterogeneity among molecular subtypes in colorectal cancer

Weng

Cui

et al. 2023

Preprint

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Background The intricate crosstalk of various cell death forms was recently implicated in cancers, laying a foundation for exploring the association between cell death and cancers. Recent evidence has demonstrated that biological networks outperformsnapshot gene expression profiles at discovering promising biomarkers or heterogenous molecular subtypes across different cancer types. In order to investigate the behavioral patterns of cell death-related interaction perturbation in colorectal cancer (CRC), this study constructed the interaction-perturbation network consisting of 11 cell death pathways and further revealed four cell death network (CDN) derived subtypes (CDN1-4). Methods We constructed a perturbation matrix of 11 cell death pathways by using colorectal cancer data from TCGA and GTEx, from which four CDNs were decoded and validated by three GEO datasets. Results Four subtypes were well characterized and displayed distinct clinical and molecular features: (1) CDN1: elevated proliferative activity, frequent KRAS mutations, immune desert, and high tumor purity; (2) CDN2: stronger immune activation, best prognosis, high BRAF mutation frequency, high mutational burden, moderate proliferative activity, neoantigen burden, microsatellite instability, and might be sensitive to immunotherapy sensitivity; (3) CDN3: metabolically hyperactive, immune desert, and moderate prognosis; (4) CDN4: stroma-rich, worst prognosis, immune-suppressed advanced stage, strong tumor invasion, stem cell-like, high levels of EMT and TGF-β signaling, and AOC3 considered as a potentially predictive molecule for CDN4. Conclusions In general, based on the construction of the cell death crosstalk network, which is more stable and effective than gene features, our study established four stable CRC molecular subtypes that could predict prognosis and guided treatment.

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Glucose starvation greatly enhances antiproliferative and antiestrogenic potency of oligomycin A in MCF-7 breast cancer cells

Cited by 5 publications

References 58 publications

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5

Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy

Crosstalk of cell death pathways implicates heterogeneity among molecular subtypes in colorectal cancer

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