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

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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.

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Author notes

  1. Daniel M. Brown

    Present address: Bristol-Myers Squibb - PRI, Natural Products -114, Wallingford, Connecticut, 06492, USA

Authors and Affiliations

  1. Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

    Emily Pisha, Heebyung Chai, Ik-Soo Lee, Norman R. Farnsworth, Geoffrey A. Cordell, Christopher W.W. Beecher, Harry H.S. Fong, A. Douglas Kinghorn & John M. Pezzuto

  2. Department of Pharmacy, University of Zimbabwe, Harare, Zimbabwe

    Tangai E. Chagwedera

  3. Chemistry and Life Sciences Division, Research Triangle Institute, Research Triangle Park, North Carolina, 27709, USA

    Daniel M. Brown, Mansukh C. Wani & Monroe E. Wall

  4. Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612, USA

    Tina J. Hieken, Tapas K. Das Gupta & John M. Pezzuto

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Pisha, E., Chai, H., Lee, IS. et al. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med 1, 1046–1051 (1995). https://doi.org/10.1038/nm1095-1046

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  • DOI: https://doi.org/10.1038/nm1095-1046

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