Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis

Nat Med. 1995 Oct;1(10):1046-51. doi: 10.1038/nm1095-1046.


As a result of bioassay-guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma-specific cytotoxic agent. In follow-up studies conducted with athymic mice carrying human melanomas, tumour growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumour activity was mediated by the induction of apoptosis. Betulinic acid is inexpensive and available in abundant supply from common natural sources, notably the bark of white birch trees. The compound is currently undergoing preclinical development for the treatment or prevention of malignant melanoma.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis
  • Betulinic Acid
  • DNA Damage*
  • Growth Inhibitors / pharmacology*
  • Guanidines / pharmacology
  • Humans
  • Liver Neoplasms / pathology
  • Melanoma / pathology*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Nude
  • Pentacyclic Triterpenes
  • Putrescine / pharmacology
  • Skin Neoplasms / pathology
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured / drug effects


  • Antineoplastic Agents, Phytogenic
  • Growth Inhibitors
  • Guanidines
  • Pentacyclic Triterpenes
  • Triterpenes
  • pimagedine
  • Putrescine
  • Betulinic Acid