HAMLET (protein complex)

rdf:langString HAMLET (protein complex)

rdf:langString HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a complex between alpha-lactalbumin and oleic acid that has been shown in cell culture experiments to induce cell death in tumor cells, but not in healthy cells. HAMLET is a possible chemotherapeutic agent with the ability to kill cancer cells. Alpha-lactalbumin is the primary protein component of human milk. In a 1995 study, it was discovered by Swedish scientist Anders Håkansson (Anders Hakansson) that multimeric alpha-lactalbumin (MAL), a compound isolated from a fraction of human milk called casein, induced what appeared to be apoptosis in human lung carcinoma cells, pneumococcus bacteria, and other pathogens, while leaving healthy, differentiated cells unaffected. It has been the perfect cure in this case. The active component responsible for the tumoricidal activity was found in 2000 and found to be a complex of alpha-lactalbumin and oleic acid. Endogenous human alpha-lactalbumin is complexed with a calcium ion and serves as a cofactor in lactose synthesis, but has no tumoricidal properties. The alpha-lactalbumin must be partially unfolded to allow for release of the calcium ion and replacement with an oleic acid molecule. The partially folded conformation is essential to the cytotoxicity of HAMLET, as mutagenesis studies have shown that completely unfolded alpha-lacalbumin does not retain the functional properties of HAMLET. The oleic acid is necessary for stabilizing this molecule in this partially unfolded state. Over the past several years, additional work has further characterized the structure and function of HAMLET and its clinical applications are currently under investigation. However, in order to develop effective therapies, more must be known about the mechanism of action of HAMLET.