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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

HAMLET

lactalbumin

cancer

apoptosis

apoptosis-like

programmed cell death

alpha- histone

p53

bcl-2

caspase

glioblastoma

HPV

Publication and Content Type

kap (subject category)

vet (subject category)