Angiotensin II induces oxidative stress in prostate cancer.
Angiotensin II has been shown to be a cytokine especially acting as a growth factor. A local renin-angiotensin system has been identified in the prostate gland, and the physiologic function of angiotensin II seems to be similar in prostate cancer, as we previously reported. In the present study, we explored the biological role of angiotensin II in oxidative stress of prostate cancer cells. Activated Akt was determined, and the expression of oxidative stress-related proteins (p47phox, manganese superoxide dismutase 2, glutathione peroxidase) was examined by Western blotting in LNCaP cells, which were stimulated with angiotensin II and/or an angiotensin II receptor type 1 blocker, candesartan. To examine DNA damage induced by angiotensin II, 8-hydroxy-2'-deoxyguanosine was determined, and Western blots were analyzed to detect checkpoint proteins including p53, Chk2, and cdc2. Immunocytochemical studies of inducible nitric oxide synthase and superoxide anion radical (O(2)(-)) were done in LNCaP cells stimulated with angiotensin II. The phosphorylation of Akt was induced by angiotensin II treatment and inhibited by candesartan, as well as by LY294002, an inhibitor of phosphoinositide 3-kinase. Oxidative stress-related proteins were up-regulated by angiotensin II and inhibited by pretreatment with candesartan or catalase. The level of 8-hydroxy-2'-deoxyguanosine was increased by angiotensin II and conversely decreased by candesartan. Immunocytochemical studies showed that angiotensin II enhanced an inflammatory marker, inducible nitric oxide synthase, and the production of O(2)(-) radical. The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed.
Uemura
Hiroji
H
Department of Urology, Yokohama City University School of Medicine, Yokohama, Japan. hu0428@med.yokohama-cu.ac.jp
Ishiguro
Hitoshi
H
Ishiguro
Yukari
Y
Hoshino
Kouji
K
Takahashi
Satoru
S
Kubota
Yoshinobu
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008954:Models, Biological; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D018797:Cell Cycle Proteins; D044140:Receptor, Angiotensin, Type 1; D013481:Superoxides; D000804:Angiotensin II; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D003849:Deoxyguanosine