HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy

J Nutr. 2005 May;135(5):1299-303. doi: 10.1093/jn/135.5.1299.

Abstract

New cancer treatments should aim to destroy tumor cells without disturbing normal tissue. HAMLET (human alpha-lactalbumin made lethal to tumor cells) offers a new molecular approach to solving this problem, because it induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. After partial unfolding and binding to oleic acid, alpha-lactalbumin forms the HAMLET complex, which enters tumor cells and freezes their metabolic machinery. The cells proceed to fragment their DNA, and they disintegrate with apoptosis-like characteristics. HAMLET kills a wide range of malignant cells in vitro and maintains this activity in vivo in patients with skin papillomas. In addition, HAMLET has striking effects on human glioblastomas in a rat xenograft model. After convection-enhanced delivery, HAMLET diffuses throughout the brain, selectively killing tumor cells and controlling tumor progression without apparent tissue toxicity. HAMLET thus shows great promise as a new therapeutic with the advantage of selectivity for tumor cells and lack of toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents*
  • Humans
  • Immunity, Innate
  • Lactalbumin / chemistry
  • Lactalbumin / immunology*
  • Lactalbumin / pharmacology
  • Milk, Human / immunology*
  • Models, Molecular
  • Protein Conformation
  • Protein Denaturation

Substances

  • Anticarcinogenic Agents
  • Lactalbumin