Anticancer effects of pyocyanin on HepG2 human hepatoma cells.
Pyocyanin, a major virulence factor produced by Pseudomonas aeruginosa, displays redox activity and damaging effects on mammalian cells. In this study, we investigated the effects of pyocyanin on the proliferation of HepG2 tumour cells. Interestingly, pyocyanin significantly inhibited cell proliferation and triggered the production of large amounts of reactive oxygen species (ROS), thereby upregulating superoxide dismutase (SOD) and catalase (CAT). Additionally, pyocyanin treatment significantly depleted reduced glutathione (GSH) and decreased the GSH/oxidized GSH (GSSG) ratio. These results supported that pyocyanin-induced cytotoxicity in HepG2 cells was mediated by acute ROS production and subsequent oxidative stress. SA-β-Gal, acridine orange (AO)/ethidium bromide (EB) double staining, caspase-3 measurements and comet assay results revealed that cell death induced by pyocyanin involved DNA damage and activation of caspase-3, accelerating cell senescence and apoptosis. Thus, our data provided insights into the mechanisms underlying pyocyanin-induced cytotoxicity and may lead to better treatment strategies for cancer.


CONCLUSIONS
Pyocyanin is a redox-active phenazine toxin. Here, we investigated the ability of pyocyanin to inhibit cancer-related phenotypes in HepG2 human hepatoma cells. Our results indicated that pyocyanin accelerated cellular senescence and apoptosis and induced oxidative stress-associated DNA damage in HepG2 cells. The potential anticancer applications of pyocyanin should be investigated further in clinical studies.
School of Environment & Biological Engineering, Nanjing University of Science & Technology, Nanjing, China.
J
J
Zhao
Y
Y
Wu
A T
AT
Alfred
P
P
Wei
S
S
Yang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011710:Pyocyanine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D011710:Pyocyanine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione
HepG2; apoptosis; oxidative stress; pyocyanin; reactive oxygen species; senescence