1. Role of nitric oxide in the response to photooxidative stress in prostate cancer cells.
- Author
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D'Este F, Della Pietra E, Badillo Pazmay GV, Xodo LE, and Rapozzi V
- Subjects
- Cell Line, Tumor, Chlorophyll analogs & derivatives, Chlorophyll toxicity, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Humans, Male, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide antagonists & inhibitors, Nitric Oxide radiation effects, Nitric Oxide Synthase Type II metabolism, Nitric Oxide Synthase Type II radiation effects, Oxidative Stress drug effects, Oxidative Stress radiation effects, Prostatic Neoplasms pathology, Reactive Oxygen Species radiation effects, Nitric Oxide physiology, Oxidative Stress physiology, Prostatic Neoplasms metabolism, Radiation-Sensitizing Agents toxicity, Reactive Oxygen Species metabolism
- Abstract
A continuous state of oxidative stress during inflammation contributes to the development of 25% of human cancers. Epithelial and inflammatory cells release reactive oxygen species (ROS) and reactive nitrogen species (RNS) that can damage DNA. ROS/RNS have biological implications in both chemoresistance and tumor recurrence. As several clinically employed anticancer drugs can generate ROS/RNS, we have addressed herein how inducible nitric oxide synthase and nitric oxide (iNOS/
• NO) affect the molecular pathways implicated in the tumor response to oxidative stress. To mimic the oxidative stress associated with chemotherapy, we used a photosensitizer (pheophorbide a) that can generate ROS/RNS in a controlled manner. We investigated how iNOS/• NO modulates the tumor response to oxidative stress by involving the NF-κB and Nrf2 molecular pathways. We found that low levels of iNOS induce the development of a more aggressive tumor population, leading to survival, recurrence and resistance. By contrast, high levels of iNOS/• NO sensitize tumor cells to oxidative treatment, causing cell growth arrest. Our analysis showed that NF-κB and Nrf2, which are activated in response to oxidative stress, communicate with each other through RKIP. For this critical role, RKIP could be an interesting target for anticancer drugs. Our study provides insight into the complex signaling response of cancer cells to oxidative treatments as well as new possibilities for the rational design of new therapeutic strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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