Cytotoxic activity of violacein in human colon cancer cells.
Several studies have shown that violacein, a purple pigment extracted from Chromobacterium violaceum, is capable to induce apoptosis in a variety of cancer cells, including those leukemia cell lines. Herein, we examined the effects of violacein on reactive oxygen species (ROS) production during the apoptotic colon cancer cell death. We demonstrate that violacein mediates ROS production followed by activation of Caspase-3, release of cytochrome c, and calcium release to citosol in Caco-2 cells. Moreover, presence of ROS scavengers such as N-acetyl-cysteine (NAC) diminishes ROS cytotoxicity induced by violacein in Caco-2 cells, indicating that violacein mediates cellular critical mechanisms in the triggering of apoptotic tumor cell death. These data also imply that violacein-induced ROS are collectively key mediators of mitochondrial membrane collapse, leading to cytochrome c release, and culminating in tumor apoptosis. Unlike in Caco-2 cells, violacein was incapable of increasing ROS levels in HT29 cells, suggesting the existence of violacein cell-type specific mechanisms. Those findings bring light to the violacein cytotoxic mechanism studies, indicating that oxidative stress play a role in the violacein-induced cytotoxicity.
de Carvalho
Daniela D
DD
Departamento de Bioquímica, IB, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil. ddc@unicamp.br
Costa
Fabio T M
FT
Duran
Nelson
N
Haun
Marcela
M
D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D007202:Indicators and Reagents; D007211:Indoles; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D045304:Cytochromes c; D053148:Caspase 3; C022616:thiazolyl blue; C063155:violacein; D002118:Calcium