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