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

Emily Pisha, Heebyung Chai, Ik Soo Lee, Tangai E. Chagwedera, Norman R. Farnsworth, Geoffrey A. Cordell, Christopher W.W. Beecher, Harry H.S. Fong, A. Douglas Kinghorn, Daniel M. Brown, Mansukh C. Wani, Monroe E. Wall, Tina J. Hieken, Tapas K.Das Gupta, John M. Pezzuto

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Abstract

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 preciinicai development for the treatment or prevention of malignant melanoma.

Original languageEnglish (US)
Pages (from-to)1046-1051
Number of pages6
JournalNature Medicine
Volume1
Issue number10
DOIs
StatePublished - Oct 1995

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pisha, E., Chai, H., Lee, I. S., Chagwedera, T. E., Farnsworth, N. R., Cordell, G. A., Beecher, C. W. W., Fong, H. H. S., Kinghorn, A. D., Brown, D. M., Wani, M. C., Wall, M. E., Hieken, T. J., Gupta, T. K. D., & Pezzuto, J. M. (1995). Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nature Medicine, 1(10), 1046-1051. https://doi.org/10.1038/nm1095-1046