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Nutritional shortage augments cisplatin-effects on murine melanoma cells
F Antunes1, G J Pereira1, M G Jasiulionis1
1Universidade Federal de São Paulo, Escola Paulista de Medicina Department of Pharmacology (EPM/UNIFESP), São Paulo, SP, Brazil.
Abstract:
Melanoma incidence increases every year worldwide and is responsible for 80% of skin cancer deaths. Due to its metastatic potential and resistance to almost any treatments such as chemo, radio, immune and targeted-therapy, the patients still have a poor prognosis, especially at metastatic stage. Considering that, it is crucial to find new therapeutic approaches to overcome melanoma resistance. Here we investigated the effect of cisplatin (CDDP), one of the chemotherapeutic agents used for melanoma treatment, in association with nutritional deprivation in murine melanoma cell lines. Cell death and autophagy were evaluated after the treatment with cisplatin, nutritional deprivation and its association using an in vitro model of murine melanocytes malignant transformation to metastatic melanoma. Our results showed that nutritional deprivation augmented cell death induced by cisplatin in melanoma cells, especially at the metastatic subtype, with slight effects on melanocytes. Mechanistic studies revealed that although autophagy was present at high levels in basal conditions in melanoma cells, was not essential for cell death process that involved mitochondrial damage, reactive oxygen species production and possible glycolysis inhibition. In conclusion, nutritional shortage in combination with chemotherapeutic drugs as cisplatin can be a valuable new therapeutic strategy to overcome melanoma resistance.
Insights
Nutritional deprivation enhances cisplatin chemotherapy effectiveness against melanoma cells, particularly metastatic types. This combination therapy offers a promising strategy to overcome treatment resistance in melanoma patients.
Area of Science:
- Oncology
- Cancer Biology
- Cellular Biology
Background:
- Melanoma incidence is rising globally, causing significant mortality.
- Melanoma exhibits high metastatic potential and resistance to conventional therapies, leading to poor patient prognosis.
- Novel therapeutic strategies are urgently needed to combat melanoma resistance.
Purpose of the Study:
- To investigate the combined effects of cisplatin (CDDP) and nutritional deprivation on melanoma cell death.
- To evaluate the role of autophagy in this combined treatment approach.
- To explore the underlying mechanisms of cell death induced by this combination therapy.
Main Methods:
- Utilized an in vitro model of murine melanocyte malignant transformation to metastatic melanoma.
- Treated cells with cisplatin, nutritional deprivation, or a combination thereof.
- Assessed cell death, autophagy levels, mitochondrial damage, reactive oxygen species (ROS) production, and glycolysis.
Main Results:
- Nutritional deprivation significantly augmented cisplatin-induced cell death in melanoma cells, especially the metastatic subtype.
- Slight effects were observed on non-malignant melanocytes.
- Autophagy was not essential for the observed cell death, which involved mitochondrial damage, ROS production, and potential glycolysis inhibition.
Conclusions:
- Combining nutritional deprivation with cisplatin represents a potential therapeutic strategy to overcome melanoma resistance.
- This approach may offer a new avenue for improving treatment outcomes in melanoma patients.
- The mechanism involves non-autophagic cell death pathways, including mitochondrial dysfunction.
