Betulinic acid reduces ultraviolet-C-induced DNA breakage in congenital melanocytic naeval cells: evidence for a potential role as a chemopreventive agent

Melanoma Res. 2001 Apr;11(2):99-104. doi: 10.1097/00008390-200104000-00003.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Betulinic Acid
  • Blotting, Western
  • Comet Assay
  • DNA / radiation effects
  • DNA Damage
  • Down-Regulation
  • Genes, Dominant
  • Genes, p53 / genetics
  • Humans
  • Melanocytes / pathology*
  • Neoplasms, Radiation-Induced / drug therapy*
  • Nevus / metabolism*
  • Pentacyclic Triterpenes
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured
  • Ultraviolet Rays*
  • rho GTP-Binding Proteins / genetics


  • Anticarcinogenic Agents
  • Antineoplastic Agents, Phytogenic
  • Pentacyclic Triterpenes
  • Triterpenes
  • DNA
  • rho GTP-Binding Proteins
  • Betulinic Acid