New tumor-killer shows great promise in suppressing cancers

A molecule  based on a natural protein present in human breast milk, which has been found to have strong and wide-ranging tumour killing properties when bound to certain lipids. Lipids are organic molecules like amino acids and carbohydrates, made up of carbon and hydrogen, and help to store energy and to form biological membranes.

The protein-lipid molecule complex, is known as HAMLET, which stands for Human Alpha-lactabumin Made Lethal to Tumour cells. It has been proven to be safe and effective as it only targets tumour cells, leaving healthy human cells intact.

HAMLET has most recently been shown to successfully suppress colon cancer in laboratory mice.

The scientists have also successfully identified and isolated specific components of HAMLET called peptide-oleate bound forms, which have the tumour-killing effect. Peptides are short chain amino acids commonly found in the human body.

These latest breakthroughs are led by Professor Catharina Svanborg and Dr Manoj Puthia from Lund University, Sweden, and Professor Gerhard Grüber from NTU's School of Biological Sciences. The HAMLET complex was first discovered by Professor Svanborg's research group.

The findings were published recently in Gut and in PLoS ONE. The researchers found that laboratory mice genetically modified to develop colon cancer, were protected to a large extent when fed with HAMLET- laced water. This suggested that HAMLET was killing emerging tumour cells faster than these cells could grow and proliferate.

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053051

New tumor-killer shows great promise in suppressing cancers

HAMLET (found in breast milk) may target molecules in specific membrane regions.....

We know that HAMLET (human α-lactalbumin made lethal to tumor cells) is a molecular complex of α-lactalbumin and oleic acid (see structure courtesy : Lunds Univ). It induces apoptosis in tumor cells, but normal differentiated cells are resistant to its effect . The activity of HAMLET was discovered by serendipity, while using human milk fractions to investigate bacteria adherence to lung carcinoma cell lines. In addition to blocking adherence, one milk fraction actually killed the cells by inducing apoptosis. Cell death was accompanied by changes in morphology, nuclear condensation, cytoplasmic blebbing, and formation of apoptotic bodies, similar to cells that undergo classical apoptosis.

Further studies showed that HAMLET comprises a protein and a fatty acid that are both found naturally in breast milk. So far, however, it has not been proven that the HAMLET complex is spontaneously formed in the milk. It is speculated, however, that HAMLET can form in the acidic environment of the babies´ stomachs. Laboratory experiments have shown that HAMLET kills 40 different types of cancer, and the researchers are studying  its effect on skin cancer, tumours in the mucous membranes and brain tumours. Importantly, HAMLET kills only cancer cells and does not affect healthy cells.

Although the substance was found several years ago, it is only now that it has been possible to test it on humans. Patients with cancer of the bladder who were treated with the substance excreted dead cancer cells in their urine after each treatment, which has given rise to hopes that it can be developed into medication for cancer care in the future.

Researchers at the University of Gothenburg are focussed on how HAMLET can be taken up into tumour cells. Researchers  lead by,  Roger Karlsson attempting to gain an in-depth understanding of how the substance interacts with cell membranes. 

In their study, researchers examined the interactions of HAMLET with in vitro generated membranes of known composition, and compared HAMLET to the native or partially unfolded, fatty acid free proteins. They also examined the effect of HAMLET on plasma membrane vesicles (PMVs) obtained from tumor cells. Researchers could show that HAMLET interacts with membranes and disturbs their integrity under physiological conditions. Binding to intact tumor cell membranes showed a patchy distribution, indicating that HAMLET may target molecules in specific membrane regions.

Researchers conclude that, HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. 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...

Ref : Roger Karlsson et.al.,  PLoS One., February 23, 2010