Glucose starvation-induced oxidative stress causes mitochondrial dysfunction and apoptosis via Prohibitin 1 upregulation in human breast cancer cells
| Autor: | Manika Pal Bhadra, Moumita Chakrabarti, Ganesh Kumar Raut, Deepika Pamarthy |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Cell Survival Apoptosis Breast Neoplasms medicine.disease_cause Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Physiology (medical) Prohibitins medicine Animals Humans Glycolysis Prohibitin Membrane Potential Mitochondrial Chemistry Xenograft Model Antitumor Assays Mitochondria Gene Expression Regulation Neoplastic Repressor Proteins Oxidative Stress 030104 developmental biology Glucose Hormone receptor Starvation Cancer cell Cancer research Female Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Free radical biologymedicine. 145 |
| ISSN: | 1873-4596 |
| Popis: | In recent years there has been an upsurge in research focusing on reprogramming cancer cells through understanding of their metabolic signatures. Alterations in mitochondrial bioenergetics and impaired mitochondrial function may serve as effective targeting strategies especially in triple-negative breast cancers (TNBCs) where hormone receptors and endocrine therapy are absent. Glucose starvation (GS) of MDA-MB-231 and MCF-7 breast cancer cells showed decrease in mitochondrial Oxygen Consumption Rate (OCR), which was rescuable to control level through addition of exogenous antioxidant N-Acetyl Cysteine (NAC). Mechanistically, GS led to increase in mitochondrial ROS and upregulation of the pleiotropic protein, Prohibitin 1 (PHB1), leading to its dissociation from Dynamin-related protein 1 (DRP1), perturbance of mitochondrial membrane potential (MMP) and triggering of the apoptosis cascade. PHB1 also reduced the invasive and migratory potential of both cell lines. We emphasize that glucose starvation remarkably sensitized the highly glycolytic metastatic TNBC cell line, MDA-MB-231 to apoptosis and decreased its migratory potential. Based on our findings, additional TNBC cell lines can be evaluated and a nutritional paradigm be proposed for anticancer therapy. |
| Databáze: | OpenAIRE |
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