Mechanisms that kill tumour cells mapped

In a major international collaboration, researchers at Lund University, who discovered HAMLET, are showing what it is that makes the substance lethal to tumour cells in particular.

Petter Storm and Professor Catharina Svanborg. Photo: Ingela Björck

HAMLET* has produced an effect on over 40 different types of cancer cells in laboratory experiments – tumours from the lungs, kidneys, prostate, ovaries and bowel, as well as melanoma, leukaemia and others. In animal experiments, it has been shown to reduce the growth of the brain tumour glioblastoma, and in human trials it has produced good results against papilloma (a type of skin cancer) and bladder cancer.

An article recently published in the journal Oncogene shows that HAMLET targets one of the most fundamental ‘oncogenes’, genes which are involved in the development of cancer. The gene is called c-Myc and is well known to all cancer researchers. HAMLET also affects the cells’ metabolism so that glycolysis – the process of making energy from sugar – is stopped.

“All tumour cells have an altered metabolism which makes them highly dependent on sugar. HAMLET affects the metabolism very quickly. In only one hour, the cell’s energy supply is turned off”, explains professor and research leader Catharina Svanborg.

Her colleague Petter Storm has not only seen HAMLET’s effect on tumour cells, but also the effect of the experiments on other cancer researchers.

“At first they were somewhat cautious. But when we had done the first experiment, their eyes lit up!” he says.

Petter Storm is talking about the Lund group’s partners at the Cold Spring Harbor Laboratory in the USA. This is a renowned laboratory for cancer research, led by Nobel Prize winner James Watson, famous as one of the discoverers of the DNA helix.

The 83-year-old Professor Watson is one of the authors of the long research article which the Lund group and its partners have now published. One part of the study in the article uses a technique developed at Cold Spring Harbor, where they have managed to destroy all the cells’ 20 000 or so genes in one single experiment. By using this method in combination with HAMLET, they have been able to prove that HAMLET targets the gene c-Myc. C-Myc in turn influences the metabolism, which explains HAMLET’s effect on this.

“We have received a lot of response to the article from colleagues around the world. Research on HAMLET is already being carried out in the United Kingdom, Russia, Italy and the US, and our new publication could further boost the interest in the substance”, says Catharina Svanborg.

HAMLET was identified in 1994, when Catharina Svanborg and her colleagues were testing the antibacterial effects of breast milk. For practical reasons, they had chosen to grow tumour cells to conduct the tests on, which produced the surprising result that many of the cells simply died.

HAMLET’s special combination of a fatty acid and a breast milk protein in a certain folding variant does not exist in a mother’s newly produced breast milk. The Lund group believes that the protein complex is not formed until the milk is in the baby’s stomach. There are also many newly formed cells in the stomach and the protein’s task could be to eliminate incorrect ones that could develop into tumour cells.

*HAMLET is a complex between a protein and a fatty acid, and the name is an acronym of “human alfa-lactalbumin made lethal to tumour cells”.

Photo of Petter Storm and Professor Catharina Svanborg.
Text and photo: Ingela Björck