1. Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocytic naeval cells: evidence for a potential role as a chemopreventive agent.
- Author
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Salti GI, Kichina JV, Das Gupta TK, Uddin S, Bratescu L, Pezzuto JM, Mehta RG, and Constantinou AI
- Subjects
- Blotting, Western, Comet Assay, DNA radiation effects, DNA Damage, Down-Regulation, Genes, Dominant, Genes, p53 genetics, Humans, Pentacyclic Triterpenes, Tumor Cells, Cultured, rho GTP-Binding Proteins genetics, Betulinic Acid, Anticarcinogenic Agents pharmacology, Antineoplastic Agents, Phytogenic pharmacology, Melanocytes pathology, Neoplasms, Radiation-Induced drug therapy, Nevus metabolism, Triterpenes pharmacology, Ultraviolet Rays
- Abstract
Melanoma transformation progresses in a multistep fashion from precursor lesions such as congenital naevi. Exposure to ultraviolet (UV) light promotes this process. Betulinic acid (BA) was identified by our group as a selective inhibitor of melanoma that functions by inducing apoptosis. The present study was designed to investigate the effect of BA and UV-C (254 nm) on cultured congenital melanocytic naevi (CMN) cells, using the single-cell gel electrophoresis (comet) assay to detect DNA damage. Exposure to UV light induced a 1.7-fold increase in CMN cells (P = 0.008) when compared with controls. When a p53 genetic suppressor element that encodes a dominant negative polypeptide (termed GSE56) was introduced into the CMN cells, the transfected cells were more sensitive to UV-induced DNA breakage. This suggests that p53 can protect against UV-induced DNA damage and subsequent melanoma transformation. Pretreatment with BA (3 microm) for 48 h resulted in a 25.5% reduction in UV-induced DNA breakage in the CMN cells (P = 0.023), but no changes were observed in the transfected cells. However, Western blot analysis revealed no changes in the p53 or p21 levels in BA-treated cells, suggesting that BA might mediate its action via a non-p53 pathway. These data indicate that BA may have an application as a chemopreventive agent in patients with congenital naevi.
- Published
- 2001
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