HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy.
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.
Gustafsson
Lotta
L
Institute of Laboratory Medicine, Department of Microbiology, Immunology and Glycobiology, Lund University, Sweden.
Hallgren
Oskar
O
Mossberg
Ann-Kristin
AK
Pettersson
Jenny
J
Fischer
Walter
W
Aronsson
Annika
A
Svanborg
Catharina
C
D016588:Anticarcinogenic Agents; D006801:Humans; D007113:Immunity, Innate; D007768:Lactalbumin / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D008895:Milk, Human / Q000276:immunology*; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation
D016588:Anticarcinogenic Agents; D007768:Lactalbumin