Long-Term Effects of Metabolic Stress on Human Malignant Melanoma Cell Line

Introduction: Tumour is a heterogeneous tissue consisting of cells with different levels of metabolic activity. Often the outer layer cells of a tumour have more optimal conditions to grow/proliferate compared to the inner cells. Objective: The aim of the current study was to study the reactions of malignant melanoma A375 cells in exposure to different levels of metabolic stress and their ability to returning to life upon re-exposure to optimum nutritional conditions. Methods: A375 cells, at early plateau phase, were exposed to media containing 10% (control), 0.5, 0.25 and 0% serum for 1 to 6 days. At 24 h intervals, the cells were tested for morphology, cell cycle distribution, cell size changes, cell count, mitochondrial function and protein content. Also, after each day of starvation, the cells were re-exposed to optimum media (10% serum) and tested again. Results: The results showed that the cells made foci structures at long-term starvation. They primarily accumulated in G1-phase and at long-term starvation, most of them entered the apoptotic state. However, before death, cell count did not decrease, even though the mitochondrial function and protein content were less than the control cells. Releasing the cells in optimum conditions could trigger cells' proliferation ability, mitochondrial function and protein content. Conclusion: The results suggest that this model of malignant melanoma has a resistant feature against sub-optimal nutritional and metabolic status and the cells can return to life with even stronger internal engines, as evidenced by higher levels of mitochondrial function and protein content.