Violacein induces cell death by triggering mitochondrial membrane hyperpolarization in vitro

Abstract

BackgroundViolacein 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.ResultsCytotoxicity 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.ConclusionsIn 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.

Disruption of Beta-Cell Mitochondrial Networks by the Orphan Nuclear Receptor Nor1/Nr4a3

“…Our data indicate that Nor1 rather increases mitochondrial membrane potential. An alternative model exists and proposes that proapoptotic stimuli could induce mitochondrial hyperpolarization, resulting in an osmotic imbalance capable of provoking outer mitochondrial membrane rupture and the release of intermembrane space proteins such as cytochrome c to induce cell death [27][28][29]. Our results dovetail with this alternative model and suggest that Nor1 causes beta-cell death via both impairment of beta-cell function and disruption of the mitochondrial network.…”

“…Cells 2020, 9, x 7 of 14 Surprisingly, Nor1 significantly increased mitochondrial membrane potential by ~30% ( Figure 2E). This is reminiscent of a model [27][28][29] in which hyperpolarization of the inner mitochondrial membrane in proapoptotic conditions is proposed to provoke mitochondrial matrix swelling and ruptures in the outer membrane. Nor1-induced changes in glucose oxidation and ATP production translated into inhibition of glucose-stimulated insulin secretion ( Figure 2F,G).…”

Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion

“…We hypothesized that CQ treatment could cause mitochondrial dysfunction, resulting in decreased electronic transportation chain (ETC) activity and therefore inhibit Asp biosynthesis (34). To test this hypothesis, we examined mitochondrial membrane potential, a marker of mitochondrial damage (35), in PDAC cells treated with CQ. Chronic, but not acute, treatment with CQ increased mitochondrial membrane potential (Fig.…”

Advances in Chromobacterium violaceum and properties of violacein-Its main secondary metabolite: A review

“…In contrast to the effects observed in other cancer cell models, such as colon cancer (de Carvalho et al, 2006) and Ehrlich ascites tumor cells (Bromberg et al, 2010), no association between oxidative stress induction and cell death was observed. Interestingly, mitochondrial membrane hyperpolarization was demonstrated in violacein-treated HeLa and MRC-5 cells, suggesting cell-type specific induction of mitochondrial dysfunction that leads to a cell death (Leal et al, 2015).…”

“…In a work by Leal et al (2015) conducted in the HeLa cervical cancer cell line, the mechanisms of violacein cytotoxicity were investigated. Cytotoxicity to HeLa cells seemed to be mediated predominantly by apoptosis.…”