Details

Autor(en) / Beteiligte

• Raut, Ganesh Kumar
• Chakrabarti, Moumita
• Pamarthy, Deepika
• Bhadra, Manika Pal

Titel

Glucose starvation-induced oxidative stress causes mitochondrial dysfunction and apoptosis via Prohibitin 1 upregulation in human breast cancer cells

Ist Teil von

• Free radical biology & medicine, 2019-12, Vol.145, p.428-441

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •Glucose starvation sensitizes the breast cancer cells to death via mitochondrial dysfunction.•Increase in ROS and PHB1 level under GS in the mitochondria leads to intrinsic apoptotic cell death.•PHB1 and DRP1 are dissociated under GS condition, causing decrease in MMP, release of cytochrome c•Upregulated PHB1 inhibits breast cancer cells migration and invasion under GS condition.