Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocytic naeval cells: Evidence for a potential role as a chemopreventive agent
Date
2001Author
Salti, G. I.Kichina, J. V.
Das Gupta, T. K.
Uddin, S.
Bratescu, L.
Pezzuto, J. M.
Mehta, R. G.
Constantinou, Andreas I.
Source
Melanoma researchVolume
11Pages
99-104Google Scholar check
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Show full item recordAbstract
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 μm) 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. © 2001 Lippincott Williams & Wilkins.