Nitric oxide donor exisulind is an effective inhibitor of murine photocarcinogenesis
Related Experiment Video
Updated: May 24, 2026
In Vivo Imaging of Reactive Oxygen Species in a Murine Wound Model
Published on: November 17, 2018
Tripti Singh1, Sandeep C Chaudhary, Puneet Kapur
1Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.
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.
Insights
Topical NO-exisulind significantly reduced UVB-induced skin tumors in mice by inhibiting proliferation and promoting apoptosis. This novel treatment also decreased tumor invasiveness, suggesting potential for skin cancer prevention and treatment.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- NO-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) exhibit anti-inflammatory, antiproliferative, and apoptosis-inducing properties in tumor cells.
- UVB radiation is a primary cause of skin cancer, necessitating effective preventative and therapeutic strategies.
Purpose of the Study:
- To investigate the efficacy of NO-exisulind in a murine model of UVB-induced skin tumors.
- To evaluate the effects of NO-exisulind on tumor growth, proliferation, apoptosis, and epithelial-mesenchymal transition (EMT).
Main Methods:
- Topical application of NO-exisulind to SKH-1 hairless mice exposed to UVB radiation.
- Assessment of tumor incidence, number, and volume.
- Analysis of proliferation markers (PCNA, cyclin D1), apoptosis markers (Bax, Bcl2, TUNEL assay), and EMT markers (Fibronectin, N-cadherin, E-cadherin, SNAI, Slug, Twist).
- Evaluation of signaling pathways (Erk1/2, p38).
Main Results:
- NO-exisulind treatment significantly reduced tumor development, number, and volume compared to controls.
- Reduced expression of proliferation markers (PCNA, cyclin D1) and increased apoptosis (elevated Bax, decreased Bcl2, more TUNEL-positive cells).
- Inhibition of EMT markers (decreased Fibronectin, N-cadherin, SNAI, Slug, Twist; increased E-cadherin) and reduced phosphorylation of Erk1/2 and p38 signaling pathways.
Conclusions:
- NO-exisulind effectively reduces UVB-induced skin tumor growth in a murine model.
- The mechanism involves blocking cell proliferation, inducing apoptosis, and inhibiting epithelial-mesenchymal transition.
- NO-exisulind demonstrates potential as a therapeutic agent for skin cancer by reducing tumor progression and invasiveness.
