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Nitric oxide donor exisulind is an effective inhibitor of murine photocarcinogenesis.

Abstract
NO-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) have been shown to have anti-inflammatory, antiproliferative and apoptosis-inducing effects in tumor cells. Herein, we have investigated the effects of NO-exisulind on the growth of UVB-induced skin tumor development in a murine model. We found that the topical treatment with NO-exisulind significantly reduced UVB-induced tumors in SKH-1 hairless mice. The tumors/tumor bearing mouse, the number of tumors/mouse and tumor volume/mouse decreased significantly (P < 0.05) as compared with vehicle-treated and UVB-irradiated positive controls. Consistently, NO-exisulind-treated animals showed reduced expression of proliferation markers, such as PCNA and cyclin D1. These mice also manifested increased expression of proapoptotic Bax and decreased expression of antiapoptotic Bcl2 with an increase in the number of TUNEL-positive cells in tumors. We also investigated whether NO-exisulind-treated tumors are less invasive and progress less efficiently from benign to malignant carcinomas. For this, tumors were stained for various epithelial-mesenchymal transition (EMT) markers. NO-exisulind decreased the expression of mesenchymal markers, such as Fibronectin, N-cadherin, SNAI, Slug and Twist and enhanced the epithelial marker E-cadherin. Similarly, UVB-induced phosphorylation of Erk1/2 and p38 was decreased in NO-exisulind-treated animals. These data suggest that NO-exisulind reduces tumor growth and inhibits tumor progression by blocking proliferation, inducing apoptosis and reducing EMT.
AuthorsTripti Singh, Sandeep C Chaudhary, Puneet Kapur, Zhiping Weng, Craig A Elmets, Levy Kopelovich, Mohammad Athar
JournalPhotochemistry and photobiology (Photochem Photobiol) 2012 Sep-Oct Vol. 88 Issue 5 Pg. 1141-8 ISSN: 1751-1097 [Electronic] United States
PMID22364235 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers, Tumor
  • Cadherins
  • Cdh2 protein, mouse
  • Fibronectins
  • Nitric Oxide Donors
  • Transcription Factors
  • Twist Transcription Factor
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • snail family transcription factors
  • Cyclin D1
  • Sulindac
  • sulindac sulfone
Topics
  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Biomarkers, Tumor (genetics, metabolism)
  • Cadherins (genetics, metabolism)
  • Carcinoma (drug therapy, metabolism, pathology)
  • Cyclin D1 (genetics, metabolism)
  • Epithelial-Mesenchymal Transition (drug effects, radiation effects)
  • Fibronectins (genetics, metabolism)
  • Gene Expression (drug effects, radiation effects)
  • Mice
  • Mice, Hairless
  • Nitric Oxide Donors (pharmacology)
  • Signal Transduction (drug effects, radiation effects)
  • Skin (drug effects, pathology, radiation effects)
  • Skin Neoplasms (drug therapy, metabolism, pathology)
  • Snails (genetics, metabolism)
  • Sulindac (analogs & derivatives, pharmacology)
  • Transcription Factors (genetics, metabolism)
  • Twist Transcription Factor (genetics, metabolism)
  • Ultraviolet Rays (adverse effects)
  • bcl-2-Associated X Protein (genetics, metabolism)
  • bcl-Associated Death Protein (genetics, metabolism)

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