Oxidative stress and cyclooxygenase activity in prostate carcinogenesis: targets for chemopreventive strategies.
Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. Oxidative stress may be linked to the effects of androgens, anti-oxidant systems and the pre-malignant condition, high-grade prostatic intraepithelial neoplasia. Cyclooxygenase-2 activity has been linked with prostate carcinogenesis. Evidence suggests that oxidative stress and cyclo-oxygenase-2 activity may be mechanistically linked. Agents such as anti-oxidants and cyclo-oxgenase-2 inhibitors may be of value in the chemoprevention of prostate cancer. The feasibility of intervention with such agents will depend on the development and validation of biomarkers for clinical trials, particularly markers of oxidative damage caused by reactive oxygen species (ROS). A greater understanding of the molecular events associated with oxidative stress will enhance the development of such biomarkers and should result in better strategies for the chemoprevention of prostate cancer.
Pathak
S K
SK
Division of Urology, Clinical Sciences Unit, Leicester General Hospital, University of Leicester, Gwendolen Road, Leicester LE5 4PW, UK.
Sharma
R A
RA
Steward
W P
WP
Mellon
J K
JK
Griffiths
T R L
TR
Gescher
A J
AJ
D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D018736:DNA Adducts / Q000378:metabolism; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*
D000728:Androgens; D014408:Biomarkers, Tumor; D018736:DNA Adducts; D008565:Membrane Proteins; D008084:Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases