Human α-lactalbumin made lethal to tumor cell death (HAMLET) mediates amyloid precursor protein (APP) in inducing cell death.

Abstract

HAMLET (Human α-lactalbumin made lethal to tumor cells) is a complex formed by the binding of partially unfolded α-lactalbumin and oleic acid in an ion exchange chromatography. It possesses tumoricidal activity by triggering tumor cell death, however, leaving the healthy differentiated cells unaffected. The effect of HAMLET was hypothesised to be dependent on the cell endogenous amyloid precursor protein (APP) expression level. Through the regulation of APP processing, the release of amyloid intracellular cytoplasmic domain (AICD) might contribute to cell death. HAMLET-treated cells were analysed using cell morphology studies, WST-1 assay (cell viability assay) and western blot. Our results show that HAMLET triggers cell death by increasing the expressions of APP, p-APP, presenilin 1(PS1) and p-JNK (c-jun N-terminal kinase). Our γ-secretase inhibitor study, as well as APP overexpression study, further confirms that HAMLET regulates APP processing, thus inducing tumor cell death. In this study, we discovered a novel pathway which could contribute greatly to clinical applications in cancer.