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Lycopene alters intracellular glutathione status and antioxidant/phase II detoxifying enzymes in human prostate cancer cells
Author(s) -
Marisiddaiah Raju,
Gong Xiaoming,
Wiener Doris,
Rubin Lewis P
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.344.5
Subject(s) - lycopene , antioxidant , prostate cancer , glutathione , intracellular , enzyme , chemistry , biochemistry , pharmacology , cancer , medicine
Lcopene, and its metabolites, can reduce prostate cancer (PC) growth. Normal and cancerous prostate cells and subcellular compartments have different redox states. Exposure to lycopene alters cellular pathways governing cellular redox and antioxidant state. Androgen‐dependent (C4‐2) and resistant (DU145) human PC cells were treated with 0, 1 or 3 μM lycopene. Glutathione synthesizing genes glutamylcysteine synthetase (catalytic subunit, GCLC, modulatory subunit, GCLM) and glutathione synthetase (GSS) were assayed by qRT‐PCR and western blot. Parallel analyses were performed for glutathione S‐transferase (GST‐π), NADPH:quinone oxidoreductase (NQO1) and nuclear factor E2‐related factor 2 (Nrf2). We also studied PC cells transfected with a carotene 9′,10′‐monooxygenase (CMO2) expression vector. Lycopene treatment: (1) significantly enhanced GCL expression in DU145>C4‐2 cells; (2) had no effects on GSS expression; and (3) increased the cellular glutathione level in both cell lines (DU145>C4‐2). Lycopene treatment in cells overexpressing CMO2 increased cellular glutathione levels. GCL protein levels were reduced in C4‐2 cells compared to DU145 cells at higher lycopene doses (5 and 10 μM). Lycopene treatment similarly induced GST‐π, NQO1 and Nrf2 expression (DU145>C4‐2), further supporting the role of lycopene in neutralizing reactive oxygen species. Pre‐treatment with buthionine sulfoximine, a GCL inhibitor, reduced cellular glutathione and decreased expression of the GCLC and GCLM subunits. Subsequent lycopene treatment reinduced GCL expression in DU145 cells. Lycopene regulates the antioxidant functions differently in PC cell types. These findings are consistent with other data pointing to the protective effect on early‐stage (androgen‐dependent) PC. An important molecular mechanism may be action on Nrf2‐mediated phase II detoxifying/antioxidant enzymes. Grant Funding Source : NIH HD42174, Muma Family Endowment