Oleocanthal Induces Mitochondrial Dysfunction in Breast Cancer Cell Lines Depending on c-MET Expression

Oleocanthal (OC), an anti-inflammatory and antioxidant phenolic compound exclusively found in extra virgin olive oil (EVOO), has emerged as a potential anticancer agent through multiple mechanisms of action, yet its impact on key processes such as cellular metabolism remains insufficiently characterized. Here, we investigated the metabolic and mitochondrial responses to OC across different breast cancer molecular subtypes. Triple-negative (MDA-MB-231) and luminal (MCF7, T47D) breast cancer cell lines were treated with OC to evaluate cell viability, cell cycle progression, metabolic enzyme expression, mitochondrial respiration, and mitochondrial network organization. OC responsiveness differed, being highest in MDA-MB-231 and lowest in T47D cells. Lactate dehydrogenase levels decreased in all cell lines, while mitochondrial response varied. MDA-MB-231 mitochondrial function was fully impaired, while MCF7 cells showed increased respiratory activity, with marked mitochondrial fragmentation, and T47D cells largely preserved mitochondrial integrity and function. Notably, the magnitude of OC effects correlated with MET expression, an established target of OC and a prognostic factor associated with reduced relapse-free survival within the triple-negative subtype. Collectively, these findings identify OC as a modulator of cancer cell metabolism and mitochondrial dynamics, with particular relevance in MET-high triple-negative breast cancers.