Human Milk: Excellent Anticancer Alternative

In human milk α-lactalbumin is one of the main proteins which harbors tumor-selective capabilities, named human α-lactalbumin made lethal to tumor cells (HAMLET). HAMLET is formed by binding of α-lactalbumin with oleic acid resulting in release of its Ca2+ ion and a folding change. It induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. It has the capability to enter efficiently tumor cells and to accumulate in their nuclei, mitochondria, endoplasmic reticulum and proteasomes. HAMLET activates the caspase pathways by release of cytochrome c. In the tumor nuclei, HAMLET associates with histones resulting in an irreversible disruption of the chromatin organization which is crucial for its tumor-selective apoptosis induction. It also activates 20S proteasomes, which also contributes to cell death. HAMLET induces tumor-selective apoptosis in a p53 independent manner. 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. HAMLET thus shows great promise as a new therapeutic with the advantage of selectivity for tumor cells and lack of toxicity.