当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF CANCER期刊下所有文献 > Reactive oxygen species-mediated regulation of eNOS and iNOS expression in multicellular prostate tumor spheroids.

Reactive oxygen species-mediated regulation of eNOS and iNOS expression in multicellular prostate tumor spheroids.

Abstract：

:Nitric oxide (NO) generated by either endothelial nitric oxide synthase (eNOS) or inducible nitric oxide synthase (iNOS) may be involved in prostate tumorigenesis through the inhibition of reactive oxygen species (ROS)-induced apoptosis. Multicellular DU-145 prostate tumor spheroids endogenously generated NO that paralleled the production of ROS. With increasing spheroid size, eNOS expression was downregulated, whereas an upregulation of iNOS expression was observed. In parallel, NO generation declined, as evaluated by the NO indicator diaminofluorescein-2 diacetate (DAF-2DA), suggesting that NO generation in DU-145 tumor spheroids is mainly mediated by eNOS. Elevation of ROS by treatment of tumor spheroids with either buthionine sulfoximine (BSO) or hydrogen peroxide resulted in upregulation of eNOS, whereas iNOS was downregulated. Furthermore, eNOS expression was increased by epidermal growth factor (EGF) in a redox-sensitive manner. Upregulation of eNOS after treatment with hydrogen peroxide was apparently transduced through receptor tyrosine kinase signaling pathways since it was abolished by the protein kinase C (PKC) inhibitor bisindolylmaleimide-1 (BIM-1), the p21(ras) inhibitor S-trans-trans-farnesylthiosalicylic acid (FTS), the c-Raf inhibitor ZM 336372 and PD98059, which inhibits ERK1/2 activation. Endogenous NO may serve to escape from oxidative stress-induced apoptosis since treatment of tumor spheroids with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide (carboxy-PTIO) as well as the NO synthase inhibitor N-omega-amino-L-arginine (L-NAA) increased cleaved caspase-3. Consequently, lowering intracellular NO levels with either L-NAA or PTIO significantly raised ROS levels, indicating that endogenously generated NO may play a role as a ROS scavenger, thereby protecting exponentially growing tumor spheroids from ROS-induced apoptosis.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Wartenberg M,Schallenberg M,Hescheler J,Sauer H

doi

10.1002/ijc.10928

keywords:

subject

Has Abstract

pub_date

2003-04-10 00:00:00

pages

274-82

issue

eissn

0020-7136

issn

1097-0215

journal_volume

104

pub_type

杂志文章

在线工具

Reactive oxygen species-mediated regulation of eNOS and iNOS expression in multicellular prostate tumor spheroids.