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The Impact of Olive Oil Compounds on the Metabolic Reprogramming of Cutaneous Melanoma Cell Models
Cheila Brito1, Ana Tomás1, Sandra Silva2
1Unidade de Investigação em Patobiologia Molecular (UIPM) do Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., 1099-023 Lisboa, Portugal.
Abstract:
Cutaneous melanoma is the deadliest type of skin cancer, characterized by a high molecular and metabolic heterogeneity which contributes to therapy resistance. Despite advances in treatment, more efficient therapies are needed. Olive oil compounds have been described as having anti-cancer properties. Here, we clarified the cytotoxic potential of oleic acid, homovanillyl alcohol, and hydroxytyrosol on melanoma cells. Metabolic viability was determined 48 h post treatment of A375 and MNT1 cells. Metabolic gene expression was assessed by qRT-PCR and Mitogen-Activated Protein Kinase (MAPK) activation by Western blot. Hydroxytyrosol treatment (100 and 200 µM) significantly reduced A375 cell viability (p = 0.0249; p < 0.0001) which, based on the expression analysis performed, is more compatible with a predominant glycolytic profile and c-Jun N-terminal kinase (JNK) activation. By contrast, hydroxytyrosol had no effect on MNT1 cell viability, which demonstrates an enhanced oxidative metabolism and extracellular signal-regulated kinase (ERK) activation. This compound triggered cell detoxification and the use of alternative energy sources in A375 cells, inhibiting JNK and ERK pathways. Despite oleic acid and homovanillyl alcohol demonstrating no effect on melanoma cell viability, they influenced the MNT1 glycolytic rate and A375 detoxification mechanisms, respectively. Both compounds suppressed ERK activation in MNT1 cells. The distinct cell responses to olive oil compounds depend on the metabolic and molecular mechanisms preferentially activated. Hydroxytyrosol may have a cytotoxic potential in melanoma cells with predominant glycolytic metabolism and JNK activation.
Insights
Hydroxytyrosol, a compound from olive oil, shows potential to kill melanoma cells, especially those with high glycolysis and JNK activation. Other olive oil components affected cell metabolism differently.
Area of Science:
- Molecular Biology
- Cancer Research
- Nutraceuticals
Background:
- Cutaneous melanoma is a deadly skin cancer with significant therapy resistance due to its molecular and metabolic heterogeneity.
- Existing treatments for melanoma require improvement, highlighting the need for novel therapeutic strategies.
- Olive oil compounds, including hydroxytyrosol, oleic acid, and homovanillyl alcohol, have demonstrated potential anti-cancer properties.
Purpose of the Study:
- To investigate the cytotoxic effects of hydroxytyrosol, oleic acid, and homovanillyl alcohol on melanoma cell lines (A375 and MNT1).
- To elucidate the underlying metabolic and molecular mechanisms responsible for differential cell responses to these compounds.
Main Methods:
- Cell viability was assessed 48 hours post-treatment using metabolic assays.
- Gene expression related to cell metabolism was analyzed via quantitative real-time PCR (qRT-PCR).
- Mitogen-Activated Protein Kinase (MAPK) pathway activation (JNK and ERK) was evaluated using Western blot analysis.
Main Results:
- Hydroxytyrosol significantly reduced viability in A375 cells (glycolytic profile, high JNK activation) but not in MNT1 cells (oxidative metabolism, high ERK activation).
- Hydroxytyrosol induced cell detoxification and alternative energy source utilization in A375 cells, while inhibiting JNK and ERK pathways.
- Oleic acid and homovanillyl alcohol did not affect cell viability but influenced MNT1 glycolytic rate and A375 detoxification, respectively, suppressing ERK in MNT1 cells.
Conclusions:
- The anti-cancer effects of olive oil compounds on melanoma are dependent on the specific metabolic and molecular profiles of the cancer cells.
- Hydroxytyrosol exhibits cytotoxic potential against melanoma cells characterized by a predominant glycolytic metabolism and activated JNK pathway.
- Differential activation of MAPK pathways (JNK and ERK) plays a crucial role in mediating cellular responses to hydroxytyrosol and other olive oil constituents.
