Violacein induces cell death by triggering mitochondrial membrane hyperpolarization in vitro

BACKGROUND: Violacein is a purple pigment from Chromobacterium violaceum that possesses diverse biological and pharmacological properties. Among these, pro-oxidant and antioxidant activities have been suggested. However, the cytotoxic mechanisms induced by violacein are poorly understood and the improvement in knowledge regarding these cell death mechanisms will be useful to develop new therapeutic approaches. Considering this, in our work, we investigated the pro-oxidant effects of violacein in non-tumor (CHO-K1 and MRC-5) and tumor (HeLa) cell lines, searching for a better understanding of reactive oxygen species (ROS) production and cell death induction. RESULTS: Cytotoxicity induced by violacein was observed in the three cell lines; however, MRC-5 and HeLa cells were shown to be more sensitive to violacein treatment. Although punctual alterations in the antioxidant apparatus and increase in oxidative stress biomarkers was observed in some violacein concentrations, no association was found between increased oxidative stress and induction of cell death. However, the increase of mitochondrial membrane potential was observed. CONCLUSIONS: In fact, the increase of mitochondrial membrane potential in MRC-5 and HeLa cells suggests that mitochondrial membrane hyperpolarization might be the main cause of cell death triggered by violacein.