کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2112752 1084419 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pro-survival and pro-growth effects of stress-induced nitric oxide in a prostate cancer photodynamic therapy model
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Pro-survival and pro-growth effects of stress-induced nitric oxide in a prostate cancer photodynamic therapy model
چکیده انگلیسی


• NOS2 and NO were upregulated in PC-3 cancer cells after ALA and photodynamic treatment (PDT).
• NOS2 inhibition or NO scavenging increased caspase activation and apoptosis after photostress.
• NOS2 inhibition prolonged JNK and p38 MAPK activation, but negated ERK1/2 activation.
• Stress-surviving cells exhibited a NO-dependent growth spurt with greater S-phase occupancy.
• Clinical PDT efficacy may be compromised by NO’s pro-survival/pro-growth effects.

We discovered recently that human breast cancer cells subjected to photodynamic therapy (PDT)-like oxidative stress localized in mitochondria rapidly upregulated nitric oxide synthase-2 (NOS2) and nitric oxide (NO), which increased resistance to apoptotic photokilling. In this study, we asked whether human prostate cancer PC-3 cells would exploit NOS2/NO similarly and, if so, how proliferation of surviving cells might be affected. Irradiation of photosensitized PC-3 cells resulted in a rapid (<1 h), robust (∼12-fold), and prolonged (∼20 h) post-irradiation upregulation of NOS2. Caspase-3/7 activation and apoptosis were stimulated by NOS2 inhibitors and a NO scavenger, implying that induced NO was acting cytoprotectively. Cyclic GMP involvement was ruled out, whereas suppression of pro-apoptotic JNK and p38 MAPK activation was clearly implicated. Cells surviving photostress grew back ∼2-times faster than controls. NOS2 inhibition prevented this and the large increase in cell cycle S-phase occupancy observed after irradiation. Thus, photostress upregulation of NOS/NO elicited both a pro-survival and pro-growth response, both of which could compromise clinical PDT efficacy unless suppressed, e.g. by pharmacological intervention with a NOS2 inhibitor.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 343, Issue 1, 1 February 2014, Pages 115–122
نویسندگان
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