PMID- 24461061 OWN - NLM STAT- MEDLINE DCOM- 20140924 LR - 20220321 IS - 1472-765X (Electronic) IS - 0266-8254 (Linking) VI - 58 IP - 6 DP - 2014 Jun TI - Anticancer effects of pyocyanin on HepG2 human hepatoma cells. PG - 541-8 LID - 10.1111/lam.12224 [doi] AB - 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-beta-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. SIGNIFICANCE AND IMPACT OF THE STUDY: 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. CI - (c) 2014 The Society for Applied Microbiology Published 2014. This article is a U.S. Government work and is in the public domain in the USA. FAU - Zhao, J AU - Zhao J AD - School of Environment & Biological Engineering, Nanjing University of Science & Technology, Nanjing, China. FAU - Wu, Y AU - Wu Y FAU - Alfred, A T AU - Alfred AT FAU - Wei, P AU - Wei P FAU - Yang, S AU - Yang S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140307 PL - England TA - Lett Appl Microbiol JT - Letters in applied microbiology JID - 8510094 RN - 0 (Antineoplastic Agents) RN - 0 (Reactive Oxygen Species) RN - 9OQM399341 (Pyocyanine) RN - EC 1.11.1.6 (Catalase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - GAN16C9B8O (Glutathione) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Carcinoma, Hepatocellular MH - Catalase/metabolism MH - Cell Proliferation/drug effects MH - Drug Screening Assays, Antitumor MH - Glutathione/metabolism MH - Hep G2 Cells MH - Humans MH - Inhibitory Concentration 50 MH - Liver Neoplasms MH - Oxidation-Reduction MH - Oxidative Stress MH - Pyocyanine/*pharmacology MH - Reactive Oxygen Species/metabolism MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - HepG2 OT - apoptosis OT - oxidative stress OT - pyocyanin OT - reactive oxygen species OT - senescence EDAT- 2014/01/28 06:00 MHDA- 2014/09/25 06:00 CRDT- 2014/01/28 06:00 PHST- 2013/08/28 00:00 [received] PHST- 2014/01/20 00:00 [revised] PHST- 2014/01/20 00:00 [accepted] PHST- 2014/01/28 06:00 [entrez] PHST- 2014/01/28 06:00 [pubmed] PHST- 2014/09/25 06:00 [medline] AID - 10.1111/lam.12224 [doi] PST - ppublish SO - Lett Appl Microbiol. 2014 Jun;58(6):541-8. doi: 10.1111/lam.12224. Epub 2014 Mar 7.