Glucose availability dictates the fate of human melanoma cells treated with Ophiobolin A

Ophiobolin A (OPA), a natural compound produced by Bipolaris oryzae, has been shown to induce cell cycle alterations and cell death in breast, glioma and glioblastoma cancer cell lines. We previously demonstrated that in wild type and BRAF mutated (V600E) human melanoma cancer cells, 24 hours administration of OPA results in cell cycle alteration, ER-stress induction, and cell death by apoptosis. In addition, we observed different behaviours of these cells when treated with µM vs. nM concentrations of OPA, depending upon both the BRAF mutation and the availability of glucose in the growth medium. In fact, lowering the glucose concentration sensitises BRAF mutated melanoma cell lines towards OPA-induced cell death. In order to understand the molecular mechanisms underlying OPA-induced cell death in these cell lines, we performed time course analyses at different OPA concentration. Our results suggest that OPA administration induces mitochondrial damage, resulting in early MMP loss, and mitophagy induction, at different extent and with different timing in the various cell lines, again in relationship with BRAF mutation and Glucose availability.