The discovery opens up promising new possibilities for directly targeting cancer stem cells (CSC), an aggressive type of cancer cell often responsible for relapse in cancer patients.
The study was led by Javier Menendez, head of the Metabolism and Cancer group, a joint initiative by the Catalan Institute of Oncology’s (ICO) ProCURE program and the Girona Biomedical Research Institute (IDIBGI).
Five years ago, Menendez and his team started the long task of searching for new molecules with anti-CSC properties. Their method was inspired by the techniques used by pharmaceutical companies when developing new oncological drugs, first isolating and purifying the molecules before testing the effects in tumor stem cell cultures.
Investigators screened molecules to check whether they were capable of affecting the functionality of cancer stem cells, including their resistance to oncological drugs and their ability to generate new microtumors. They found these characteristics in decarboxymethyl oleuropein aglycone (DOA), a phenol-conjugated oleoside that is present in minute quantities in cold-pressed EVOO.
“Our hypothesis is that this component of olive oil, which represents no more than 2 percent of its weight but which is made up of more than 200 different components, can be used as a natural goldmine of information about new chemical structures capable of inhibiting molecular functions that are necessary for CSC,” said Menendez.
Menendez and his team found that the DOA oleoside simultaneously attacked proteins responsible for metabolism (mTOR) and epigenesis (DNMT). This dual metabolo-epigenetic mechanism effectively suppresses the functional properties of tumor stem cells, inhibiting their ability to reinitiate tumor formation.
After the initial testing phase, researchers successfully tested the molecule in lab animals. Menendez confirmed that “exposure of the cancer stem cells to specific oleosides during just a few hours was enough to completely inhibit their capacity for initiating the formation of tumors in laboratory animals.” The groundbreaking study was published in the respected medical journal Carcinogenesis, part of the Oxford University Press Group.
The third phase of the project was carried out in partnership with Mind the Byte, a bioinformatics company that specializes in drug development using novel methods such as artificial intelligence. With their help, researchers were able to map out the mechanism of action of the anti-CSC molecules. The researchers have already registered an international patent and are working on creating new molecules that mimic the anti-CSC effects of the oleosides.
For their efforts, Menendez and his colleagues received the Luis Vañó Award for Research Related to the Olive Oil Industry, presented on April 16 in Jaén by the University of Jaén in collaboration with the University of California Davis.