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Nitroglycerin: a NO donor inhibits TPA-mediated tumor promotion in murine skin
1Department of Medical Elementology and Toxicology, Hamdard University, Hamdard Nagar, New Delhi 110 062, India. prashant_trikha@hotmail.com
Abstract:
Nitroglycerin (GTN), a nitric oxide (NO) generating vasodilator has been used in the present study to assess the role of NO during tumor promotion in murine skin. Administration of GTN to 12-O tetradecanoyl phorbol 13-acetate (TPA)-treated mice resulted in a dose-dependent inhibition in the level of glutathione and the activity of antioxidant enzymes by approximately 16-40% of acetone-treated control. We also observed that GTN application led to a significant reduction in the ornithine decarboxylase (ODC) activity and decreased the rate of [3H]thymidine incorporation into epidermal DNA when compared with the acetone-treated control (P < 0.001). Treatment of DMBA-initiated TPA-promoted mice with GTN increased the latency period, decreased the tumor incidence by 32% and there was a 2-fold decrease in tumor yield (tumor/mouse) as compared with the TPA (alone)-treated group by 20 weeks. From these data, it can be concluded that NO can abrogate the toxic and tumor promoting effects of TPA and GTN can be used as a chemopreventive agent to inhibit tumorigenesis in murine skin.
Insights
Nitroglycerin (GTN), a nitric oxide (NO) generator, inhibited tumor promotion in mice. This chemopreventive agent reduced tumor incidence and yield, suggesting NO
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Nitric oxide (NO) plays a complex role in tumor promotion.
- Nitroglycerin (GTN) is a vasodilator that generates NO.
- Understanding NO's role in skin tumorigenesis is crucial for chemoprevention.
Purpose of the Study:
- To investigate the role of NO, generated by GTN, in inhibiting skin tumor promotion in mice.
- To evaluate GTN's potential as a chemopreventive agent against skin tumorigenesis.
Main Methods:
- Murine skin tumor models were used, involving 12-O tetradecanoyl phorbol 13-acetate (TPA) and/or DMBA.
- GTN was administered to TPA-treated mice to assess its effects on biochemical markers and tumor development.
- Glutathione levels, antioxidant enzyme activity, ornithine decarboxylase (ODC) activity, and DNA synthesis were measured.
Main Results:
- GTN administration dose-dependently inhibited glutathione levels and antioxidant enzyme activity.
- GTN significantly reduced ODC activity and [3H]thymidine incorporation into epidermal DNA.
- In DMBA-initiated, TPA-promoted mice, GTN increased tumor latency, decreased tumor incidence by 32%, and reduced tumor yield by 2-fold.
Conclusions:
- Nitric oxide (NO) can effectively abrogate the toxic and tumor-promoting effects of TPA in murine skin.
- Nitroglycerin (GTN) demonstrates significant chemopreventive potential against skin tumorigenesis.
- GTN's NO-generating properties may offer a novel strategy for inhibiting skin cancer development.
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