Studies - Breast Cancer

HAMLET: Substance Found in Breast Milk Kills 40 Types of Cancer Cells (POJ, 2/10)

HAMLET: Substance Found in Breast Milk Kills 40 Types of Cancer Cells

Swedish researchers have discovered that a substance found in human breast milk has the ability to kill cancer cells, according to a study published in the PLoS One Journal.

The substance known as HAMLET (Human Alpha-lactalbumin Made Lethal to Tumor cells), was discovered years ago, but has just recently been tested on humans.
In the trial conducted at Lund University in Sweden, patients suffering from bladder cancer were treated with HAMLET. After each treatment, the patients excreted dead cancer cells in their urine, healthy cells remaining intact.

Previous laboratory experiments showed that HAMLET has the ability to kill 40 different types of cancer cells, but this was the first test conducted on humans. The next step will be to test the substance on skin cancer and brain tumors.

The trial breakthrough increases the hopes that HAMLET will be developed into a cancer treatment medication in the future. [April 20, 2010, http://www.foxnews.com/story/0,2933,591289,00.html ]

Click here to read Research Article from PLoS One — "HAMLET Interacts with Lipid Membranes and Perturbs Their Structure and Integrity" published 23 February 2010, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009384

Abstract
Background

Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human α-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded α-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or specific receptors may be essential for the tumoricidal effect. This study examined whether HAMLET interacts with artificial membranes and alters membrane structure.

Methodology/Principal Findings

We show by surface plasmon resonance that HAMLET binds with high affinity to surface adherent, unilamellar vesicles of lipids with varying acyl chain composition and net charge. Fluorescence imaging revealed that HAMLET accumulates in membranes of vesicles and perturbs their structure, resulting in increased membrane fluidity. Furthermore, HAMLET disrupted membrane integrity at neutral pH and physiological conditions, as shown by fluorophore leakage experiments. These effects did not occur with either native HLA or a constitutively unfolded Cys-Ala HLA mutant (rHLAall-Ala). HAMLET also bound to plasma membrane vesicles formed from intact tumor cells, with accumulation in certain membrane areas, but the complex was not internalized by these vesicles or by the synthetic membrane vesicles.

Conclusions/Significance

The results illustrate the difference in membrane affinity between the fatty acid bound and fatty acid free forms of partially unfolded HLA and suggest that HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. Furthermore, HAMLET binding alters the morphology of the membrane and compromises its integrity, suggesting that membrane perturbation could be an initial step in inducing cell death.

["HAMLET Interacts with Lipid Membranes and Perturbs Their Structure and Integrity" published 23 February 2010, http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009384 ;
20 April 2010, http://www.foxnews.com/story/0,2933,591289,00.html ]