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Nitric oxide and endothelin-1,2 in actinic keratosis and basal cell carcinoma: changes in nitric oxide/endothelin
P Vural1, D Erzengin, M Canbaz
1Department of Biochemistry and Clinical Biochemistry, Istanbul Medical Faculty, Capa, Istanbul, Turkey.
Background:
Nitric oxide (NO) is an inorganic free radical gas which has cytostatic/cytotoxic actions in tumoral tissues, including gynecologic, breast, and colon cancer. Nitric oxide is also a multifunctional signaling molecule active in many cells of the body, including endothelial cells, macrophages, monocytes, hepatocytes, mast cells, osteoblasts, and astrocytes. Endothelin-1 (ET-1) is a 21-amino acid peptide that stimulates the proliferation of vascular smooth muscle cells, fibroblasts, and keratinocytes, and plays a role in the expression of proto-oncogenes (c-myc, c-fos), which precedes cell proliferation. Similar to NO, ET is secreted by different cell types, including macrophages, monocytes, hepatocytes, endothelial cells, vascular smooth muscle cells, and various tumor cells. Elevated ET-1 levels are observed in pulmonary, hepatocellular, and prostate cancers. Actinic keratosis (AK) and basal cell carcinoma (BCC) are common skin tumors with accentuated hyperkeratinization, hyperpigmentation, and keratinocyte proliferation.
Aim:
To investigate plasma NOx (nitrite/nitrate -- the end products of NO metabolism), ET, and the NOx/ET ratio in patients with AK and BCC in comparison with healthy controls.
Methods:
NOx, ET, and the NOx/ET ratio were measured in 13 patients with AK, 12 patients with BCC, and in 16 healthy controls.
Results:
Data analysis indicated a significant increase in plasma NOx, ET, and NOx/ET values in BCC patients in comparison with controls (P < 0.001, P < 0.05 and P < 0.001, respectively). Plasma ET levels in AK were also increased in comparison with controls (P < 0.001). When the two study groups (AK and BCC) were compared, a significant increase (P < 0.001) in the NOx/ET ratio in BCC was found.
Conclusions:
The increased plasma ET and NOx levels in AK and, especially, BCC are probably the result of and/or reason for the accentuated hyperkeratinization, hyperpigmentation, and keratinocyte proliferation. The increased production of ET and NO by keratinocytes may function as growth and cytotoxic factors and potential mitogens, and may accelerate further proliferation of these skin tumors. In addition, the increased NOx/ET ratio probably reflects a disturbed equilibrium between these two substances, leading to cell damage and tumor promotion and proliferation.
Insights
Plasma levels of nitric oxide (NOx) and endothelin-1 (ET) are elevated in skin cancer patients. The increased NOx/ET ratio in basal cell carcinoma (BCC) suggests a disturbed equilibrium contributing to tumor proliferation.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- Nitric oxide (NO) exhibits cytostatic/cytotoxic effects in tumors and acts as a signaling molecule.
- Endothelin-1 (ET-1) promotes cell proliferation and is implicated in proto-oncogene expression.
- Both NO and ET-1 are produced by various cell types, and elevated ET-1 is linked to several cancers.
Purpose of the Study:
- To compare plasma nitric oxide metabolites (NOx) and endothelin (ET) levels, along with the NOx/ET ratio, in patients with actinic keratosis (AK) and basal cell carcinoma (BCC) versus healthy controls.
Main Methods:
- Plasma NOx, ET, and the NOx/ET ratio were quantified.
- Measurements were performed in 13 AK patients, 12 BCC patients, and 16 healthy controls.
Main Results:
- BCC patients showed significantly increased plasma NOx, ET, and NOx/ET ratios compared to controls.
- AK patients exhibited significantly elevated plasma ET levels compared to controls.
- The NOx/ET ratio was significantly higher in BCC patients than in AK patients.
Conclusions:
- Elevated plasma ET and NOx in AK and BCC likely contribute to hyperkeratinization, hyperpigmentation, and keratinocyte proliferation.
- Increased ET and NO production by keratinocytes may act as growth factors, cytotoxic agents, and mitogens, accelerating skin tumor progression.
- The elevated NOx/ET ratio in BCC suggests an imbalance between these factors, potentially promoting cell damage and tumor growth.
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