Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with low 5-year survival rates, high 3-year recurrence rates, and no known therapeutic targets. Recent studies have indicated TNBCs possess an altered metabolic state with higher rates of glycolysis, mitochondrial oxidative phosphorylation (OXPHOS), and increased generation and utilization of TCA cycle intermediates. Here we utilized a label-free quantitative proteomics approach to investigate the effects of a methanolic extract from the plant Lippia origanoides (L42) on MDA-MB-231 TNBC cells. L42 dysregulated mitochondrial OXPHOS by targeting Complex I of the electron transport chain and suppressed cellular metabolism by targeting key TCA cycle enzymes and mitochondrial lipid and amino acid metabolic pathways. Our study also revealed that treatment with L42 was seen to activate the stress response, and pathways related to cell cycle progression and DNA repair. Overall, our results reveal new compelling evidence that L42 triggers rapid, irreversible apoptosis in MDA-MB-231 cells by effectively 'starving' the cells of metabolites and ATP. We continue to study the specific bioactive components of L42 in the search for novel, highly effective mitochondrial inhibitors to selectively target TNBC.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Lippia origanoides, triple-negative breast cancer, cancer metabolism
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Principal Investigators: (in alphabetical order) |
Ignacio Camarillo, Purdue University, USA |
| Submitting User: | ramanv |
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