Effect of antioxidants on androgen-induced AP-1 and NF-κB DNA-binding activity in prostate carcinoma cells

被引:81
作者
Ripple, MO
Henry, WF
Schwarze, SR
Wilding, G
Weindruch, R
机构
[1] Univ Wisconsin, Dept Med, Inst Aging, Madison, WI 53792 USA
[2] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA
[3] Univ Wisconsin, Dept Med, Ctr Comprehens Canc, Madison, WI USA
[4] Univ Wisconsin, Inst Aging, Ctr Geriatr Res Educ & Clin, William S Middleton Mem Vet Hosp, Madison, WI USA
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 1999年 / 91卷 / 14期
关键词
D O I
10.1093/jnci/91.14.1227
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Previous studies have suggested that male hormones (androgens) and certain forms of oxygen (reactive oxygen species) are linked to the development of prostate cancer. We hypothesized that androgens contribute to prostate carcinogenesis by increasing oxidative stress. We further hypothesized that antioxidants reduce prostate cancer risk by modulating androgen effects on cellular processes. Methods: To test these hypotheses, we looked for 1) a change in the level of reactive oxygen species in the presence of androgens, 2) androgen-induced binding activity of transcriptional activators AP-1 and NF-kappa B, whose activities are known to be altered during cell proliferation, and 3) the effect of antioxidants on androgen-induced transcription factor binding. Results: Physiologic concentrations (1 nM) of 5 alpha-dihydrotestosterone or 1-10 nM R1881, a synthetic androgen, produced sustained elevation of AP-1 and NF-kappa B DNA-binding activity in LNCaP cells, an androgen-responsive human prostate carcinoma cell line. Androgen-independent DU145 cells (another human prostate carcinoma cell line) were unaffected by R1881 treatment, AP-1-binding activity increased 5 hours after 1 nM R1881 treatment; NF-kappa B DNA-binding activity increased after 36 hours, Both activities remained elevated for at least 120 hours. Nuclear AP-1 and NF-kappa B protein levels were not elevated. Antioxidant vitamins C plus E blocked both androgen-induced DNA-binding activity and production of reactive oxygen species. Conclusion: Physiologic concentrations of androgens induce production of reactive oxygen species and cause prolonged AP-1 and NF-kappa B DNA-binding activities, which are diminished by vitamins C and E.
引用
收藏
页码:1227 / 1232
页数:6
相关论文
共 49 条
[1]   REDOX REGULATION OF FOS AND JUN DNA-BINDING ACTIVITY INVITRO [J].
ABATE, C ;
PATEL, L ;
RAUSCHER, FJ ;
CURRAN, T .
SCIENCE, 1990, 249 (4973) :1157-1161
[2]   A RAPID MICROPREPARATION TECHNIQUE FOR EXTRACTION OF DNA-BINDING PROTEINS FROM LIMITING NUMBERS OF MAMMALIAN-CELLS [J].
ANDREWS, NC ;
FALLER, DV .
NUCLEIC ACIDS RESEARCH, 1991, 19 (09) :2499-2499
[3]   THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION [J].
ANGEL, P ;
KARIN, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) :129-157
[4]  
BAEUERLE PA, 1994, ANNU REV IMMUNOL, V12, P141, DOI 10.1146/annurev.immunol.12.1.141
[5]   ADENOCARCINOMAS OF THE PROSTATE INDUCED BY N-NITROSO-N-METHYLUREA IN RATS PRETREATED WITH CYPROTERONE-ACETATE AND TESTOSTERONE [J].
BOSLAND, MC ;
PRINSEN, MK ;
KROES, R .
CANCER LETTERS, 1983, 18 (01) :69-78
[6]   c-Jun can mediate androgen receptor-induced transactivation [J].
Bubulya, A ;
Wise, SC ;
Shen, XQ ;
Burmeister, LA ;
Shemshedini, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (40) :24583-24589
[7]   PROOXIDANT STATES AND TUMOR PROMOTION [J].
CERUTTI, PA .
SCIENCE, 1985, 227 (4685) :375-381
[8]  
CLARK LC, 1998, FEBS P
[9]   LIPID-PEROXIDATION - A COMMON PATHOGENETIC MECHANISM [J].
DARGEL, R .
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, 1992, 44 (04) :169-181
[10]  
FEIG DI, 1994, CANCER RES, V54, pS1890