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Oncology Can cancer cells be programmed to undergo programmed cell death?
Cancer cells are able to grow particularly fast, which is due to "a very specific and strongly altered energy metabolism", scientists from the Medical University of Graz (MedUni Graz) report on their current study results. This change in energy metabolism could also facilitate the induction of so-called programmed cell death in cancer cells and thus open up new options in cancer therapy. The researchers published their results in the specialist journals "Nature Communications" and "Cellular Physiology and Biochemistry".
"Cancer cells are true masters of efficiency," says MedUni Graz. Due to the changed energy metabolism of the cells, their uncontrolled growth is made possible in the first place. The research team at MedUni Graz has now been able to prove in its current research "which changes in the calcium balance of cellular power plants, the mitochondria and the cancer cells contribute to their efficiency." The results also show how "by manipulating the cellular processes, the mitochondrial Calcium regulate the controlled cell death of tumor cells, "reports MedUni Vienna.
Researchers at MedUni Graz have discovered a possible approach to sending cancer cells into programmed cell death. (Picture: Juan Gärtner / fotolia.com) Researched energy metabolism of cancer cells
In tumor diseases, the originally dreaded cancer cells develop from originally healthy cells, which are characterized by cell growth regardless of the surrounding tissue, explain the scientists. The spread of cancer cells eventually destroys the integrity of the surrounding tissue. The team around Professor Wolfgang Graier from the Institute of Molecular Biology and Biochemistry at the Medical University of Graz has been researching the differences in the energy metabolism of cancer cells and healthy body cells, which form the basis for the rapid growth of tumors.
Altered mitochondrial activity of the tumor cells
In the current study, the researchers took a closer look at the differences between tumor cells and healthy cells in terms of mitochondrial activity. In particular, the inclusion of calcium in the mitochondrion was the focus. The mitochondria are found in almost all body cells and as power plants of the cell they produce the energy molecule adenosine triphosphate (ATP), which represents the most important "fuel" for human life, says Professor Graier. In addition, the highly dynamic organelles are in intensive interaction with the largest intracellular Ca2 + storage, the endoplasmic reticulum, the expert explains.
Absorption of calcium in the mitochondria
The uptake of calcium into the mitochondria is a crucial process for the activation of mitochondrial respiration, which underlies the generation of ATP in these organelles, reports MedUni Graz. The researchers were able to show that the calcium uptake into the mitochondria is severely impaired by the methylation of the regulatory protein MICU1 and that it is only due to the interaction of the MICU1 with the Uncoupling Protein 2 (UCP2) for calcium uptake and activation of the Mitochondria. "Professor Graier explains that in contrast to healthy cells, cancer cells appear to have the ability to regulate mitochondrial activity by expressing UCP2.
Cancer cells vulnerable to the regulation of calcium intake
"The significance of this regulation, which is specific for cancer cells, is made clear by another publication by the Graz research group," reports MedUni Graz. In additional studies, researchers have discovered that in the cancer cells, the calcium flow from the endoplasmic reticulum to the mitochondria is greatly increased. "This increased calcium intake leads to an increased production of ATP, which allows the cancer cells to generate energy for their enormous growth," according to the MedUni Graz report. Co-author Corina Madreiter-Sokolowski emphasizes that "this trick can have a negative impact on cancer cells.".
New options for cancer therapy
Thus, the steady increase in mitochondrial calcium uptake ultimately leads to mechanisms that can lead to the death of the cancer cell. The cells apparently prevent this on the one hand on the physical proximity between the endoplasmic reticulum and the mitochondria, on the other hand, via a regulation of the expression of UCP2. If this balancing act is disturbed, as for example by the grape ingredient "resveratrol", this leads according to the researchers to a selective death of cancer cells. "These research results are promising research approaches for possible new options in cancer therapy and are currently the subject of intensive further research at the University of Graz," stresses Professor Graier. (Fp)