title: Glutathione Levels and Susceptibility to Chemically Induced Injury in Two Human Prostate Cancer Cell Lines.
abstract: More aggressive prostate cancer cells (PCCs) are often resistant to chemotherapy. Differences exist in redox status and mitochondrial metabolism that may help explain this phenomenon. Two human PCC lines, PC-3 cells (more aggressive) and LNCaP cells (less aggressive), were compared with regard to cellular glutathione (GSH) levels, susceptibility to either oxidants or GSH depletors, and expression of several proteins involved in apoptosis and stress response to test the hypothesis that more aggressive PCCs exhibit higher GSH concentrations and are relatively resistant to cytotoxicity. PC-3 cells exhibited 4.2-fold higher GSH concentration than LNCaP cells but only modest differences in acute cytotoxicity were observed at certain time points. However, only LNCaP cells underwent diamide-induced apoptosis. PC-3 cells exhibited higher levels of Bax and caspase-8 cleavage product but lower levels of Bcl-2 than LNCaP cells. However, LNCaP cells exhibited higher expression of Fas receptor (FasR) but also higher levels of several stress response and antioxidant proteins than PC-3 cells. LNCaP cells also exhibited higher levels of several mitochondrial antioxidant systems, suggesting a compensatory response. Thus, significant differences in redox status and expression of proteins involved in apoptosis and stress response may contribute to PCC aggressiveness.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA. l.h.lash@wayne.edu.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lash
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA. dputt5@yahoo.com.
authors.forename: David A
authors.initials: DA
authors.lastname: Putt
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA. adajanko@umich.edu.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Jankovich
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004198:Disease Susceptibility; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D016877:Oxidants / Q000009:adverse effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D011471:Prostatic Neoplasms / Q000378:metabolism; D017382:Reactive Oxygen Species; D014947:Wounds and Injuries / Q000139:chemically induced* / Q000378:metabolism*
chemical_list: D016877:Oxidants; D017382:Reactive Oxygen Species; D045022:Lactate Dehydrogenases; D005978:Glutathione
keywords: apoptosis; glutathione; mitochondria; oxidative stress; prostate cancer cells; stress  response