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A family of naturally occurring plant compounds traditionally used to treat cardiac problems has also shown powerful effects against cancer, and a team of scientists in Luxembourg has made progress toward understanding how it works.
The researchers, led by Prof. Marc Diederich, have identified an essential step in a cell’s internal functioning that helped them understand how these substances trigger the cell death process in a wide range of cancers.
Until now, scientists have not known how these drugs—known as CGs, for “cardiac glycosides”—acted to kill cancerous cells. This new research from the private, not-for-profit lab LBMCC (Laboratoire de biologie moleculaire et cellulaire du cancer) has revealed that the whole CG family works by causing the breakdown of a protein, called Mcl-1, that normally prevents cell death. This step, they found, is essential for triggering the demise of cancer cells, which have lost the normal ability to die and, so, continue dividing out of control.
A treatment based on a compound naturally produced by the plant
Calotropis procera shows significant anti-cancer activity.
Multiple types of cancer targeted
“Substances found in nature are a rich source of inspiration in our hunt for anti-cancer therapies,” says Dr. Claudia Cerella, lead author on the study. “When we find a molecule that seems to have potential, we need to understand how it works, in order to develop an innovative treatment based on it.”
This study focused, in particular, on one type of CG that comes from an extract of the plant Calotropis procera, a type of flowering tree or shrub native to tropical Africa and Asia. The results showed that it was active at lower concentrations than other CGs and was effective against multiple types of cancer, like lung, prostate, and breast cancer – even some typically resistant to drugs. This promising candidate, which goes by the name of UNBS1450, also had an excellent ability to target cancer cells specifically, while leaving healthy cells untouched.
The LBMCC team now needs to build on this research, which was supported by donations to Luxembourg associations Fondation de Recherche Cancer et Sang, Action LIONS Vaincre le Cancer, and the Télévie Luxembourg, among others. The next steps will be to characterize in more detail how CGs bring about the reduction in Mcl-1 that they found to be necessary for the initiation of cancer cell death, and how this process may differ between cell types. “It’s essential to understand what’s happening at the molecular level in order to, one day, use this pathway to attack cancer cells in people,” explains Dr. March Diederich, director of the LBMCC.
The cardiac glycosides may prove their worth in the fight against cancer in other ways, too. In addition to their role in triggering cell death, they seem to be involved in another form of cellular self-destruction (autophagy) and may also induce cancer cells to stop growing, as opposed to actively dying. All of the above are desirable outcomes for cancer therapy, making a better understanding of Mcl-1 an important goal in the development of future treatments.