HAMLET; a novel tool to identify apoptotic pathways in tumor cells.

Research output: Chapter in Book/Report/Conference proceedingBook chapter

Abstract

Tumor cells often carry mutations in genes that control cell survival, and become resistant to signals that trigger cell death. Yet, some cell death pathways remain intact in tumor cells. If identified, these pathways might be exploited to selectively remove tumor cells. HAMLET (human α-lactalbumin made lethal to tumor cells) is a protein-lipid complex derived from human milk that activates cell death programs in tumor cells but not in healthy differentiated cells. We use HAMLET as a tool to identify apoptosis and apoptosis-like cell death mechanisms in tumor cells and to understand if these mechanisms differ between tumor and healthy cells. HAMLET interacts with the cell surface, translocates into the cytoplasm and accumulates in cell nuclei, where it disrupts the chromatin. Recent in vivo studies have shown that HAMLET maintains the tumoricidal activity in glioblastoma, papilloma and bladder cancer models, with no significant side effects. The results suggest that HAMLET should be explored as a new therapeutic agent with selectivity for the tumor and with little toxicity for adjacent healthy tissue. Such therapies are a much-needed complement to conventional treatments, to reduce the side effects and improve the selectivity.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
  • Immunology in the medical area
  • Cell and Molecular Biology

Keywords

  • HAMLET, lactalbumin, cancer, apoptosis, apoptosis-like, programmed cell death, alpha- histone, p53, bcl-2, caspase, glioblastoma, HPV
Original languageEnglish
Title of host publicationApplication of apoptosis to cancer treatment.
EditorsSluyser Mels
PublisherSpringer
Pages223-245
ISBN (Print)978-1-4020-3303-2
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedNo