Progress in the study of the mitochondrial changes that occur with cancer
Cristina G. Pedraz/DICYT Mitochondria are organelles that play an essential role in the cell. As well as being responsible for cellular respiration, they regulate death, the signalling of calcium, the synthesis of steroids, redox homeostasis (the reduction-oxidation reaction), and cell ions. Researchers of the MitoXT (Mitochondrial Toxicology and Experimental Therapeutics) Laboratory of the Neuroscience and Cell Biology Centre of the University of Coimbra in Portugal are working essentially on assessing mitochondrial changes in cancer.
One of the researchers at the laboratory, Teresa Serafim, explains that it is a case of taking a closer look at the changes in the mitochondrial function that occur during carcinogenesis and how these changes may act as a therapeutic objective.
“Mitochondria play a vital part in the cell as they regulate various tasks such as cellular respiration (with oxygen and glucose consumption) and cell homeostasis. In cancer, as the tumour gradually grows there is a great demand for oxygen and nutrients, the result of which is the inefficient delivery of resources to the tumour cells furthest away from the blood vessels”, explains Serafim.
In this manner, with the mitochondria depending on oxygen and nutrients if they are to operate normally, if these are absent they adapt to the new situation and change their function. For example, in some types of cancer “there is decreased use of the mitochondria with a reduction in the expression of mitochondrial proteins, including the respiratory chain (those responsible for breathing) and the modification of the metabolic routes”. Under normal conditions, if a cell is deprived of oxygen and nutrients the mitochondrion triggers cell death, which does not occur in a tumour cell as the latter adapts.
Mitochondrial changes in breast cancer
One of the most recent studies of the MitoXT laboratory, which will be published in the forthcoming months, concentrates on the characterisation of the main mitochondrial changes in breast cancer cell models. In this case, the researcher reveals, the mitochondria of the breast cancer cells “have specific characteristics that we use as an objective or as therapeutic resources”.
It is known that the mitochondria of these breast tumour cells show a difference in potential of the upper membrane compared with normal cells. This means that the inside of the mitochondria of these cells is charged more negatively than that of normal cells.
“In my work group compounds with a positive charge have been designed and synthesised for the purpose of being incorporated in the tumour cells. And like a Trojan horse with a large amount inside the mitochondrion, it leads to the destruction and consequently the death of the tumour cells, a subject on which we have released several publications”, she explains.
Up to now the laboratory work has consisted of studying the tumour lines in a culture. However, "with the alterations discovered for the various cell models we intend to design and synthesise new drugs for therapeutic purposes and to carry out studies on the structure/activity of these same compounds", Serafim adds.
The next step would be to assess the mitochondrial changes in human tumour biopsies. Tumours are made up of different cell types and these cells are exposed to various types of stress (in other words there will be cells that are nearer or further away from the blood vessels, which in their turn have more or less access to oxygen and nutrients). “We intend to assess the mitochondrial changes in these cells in different conditions within the tumour and consequently to suggest a possible therapy for the different situations according to our studies on the structure-activity of compounds” , she concludes.
The MitoXT laboratory where Teresa Serafim works is part of the Mitochondria, Metabolism, and Disease Group of the Neuroscience and Cell Biology Centre. The laboratory is located in the UC Biotech Building of the Biocant Park of Cantanhede in Portugal and has some 18 members.
Serafim, T. L., Carvalho, F. S., Bernardo, T. C., Pereira, G. C., Perkins, E. et al. (2014). “New derivatives of lupane triterpenoids disturb breast cancer mitochondria and induce cell death”. Bioorganic & medicinal chemistry, 22(21), 6270-6287.