I don't have enough air…
Hypoxia helps cancer cells survive
Scientists from Lomonosov Moscow State University (Moscow) and the Karolinska Institute in Stockholm described the mechanism by which cancer cells avoid death. It turned out that the lack of oxygen disrupts the synthesis of proteins that normally kill the tumor. The results of the study, supported by a grant from the Russian Science Foundation (RNF), are published in the journal Chemico-Biological Interactions (Zhang et al., Modeling hypoxia facilitates cancer cell survival through downregulation of p53 expression).
The human body gets rid of cells whose DNA has accumulated too many random mutations with the help of programmed cell death – apoptosis. The process of self-destruction is triggered by special pro–apoptotic proteins from the Bcl-2 family, which form holes (pores) in the shell of mitochondria - the "power stations" of the cell. This leads to the fact that through such pores, the cytochrome C protein exits the mitochondria into the cytoplasm. It forms a complex with other proteins, activating enzymes that directly kill the cell.
Apoptosis is interesting because it can be used to fight cancer cells, forcing them to kill themselves. However, scientists have found that most tumors develop in conditions of hypoxia, that is, in places where little oxygen is supplied due to insufficient blood supply. Oxygen is necessary for cells for oxidative reactions and energy production in mitochondria, and if it is too little, these processes are disrupted. In addition, due to lack of oxygen, mitochondria become resistant to proteins that create pores in them, and hence to apoptosis. However, until now it was not clear which mechanism helps cancer cells to avoid self-destruction in hypoxia.
Biologists have modeled hypoxia conditions for intestinal and lung tumor cells. Cancer cells were cultured under hypoxia conditions or treated with a chemical that acted on them in the same way as the lack of oxygen. The experiment showed that this caused a decrease in the number of proteins of the Bcl-2 family, which usually create pores in mitochondria. Therefore, their shells remained intact, and cytochrome C could not enter the cytoplasm and cause apoptosis. Next, the scientists investigated the reason why the number of these proteins decreased in cancer cells. It turned out that during hypoxia, the p53 regulator protein does not work in cells, which ensures the expression (that is, reading information from the gene and protein synthesis) of Bcl-2 family proteins.
To return the tumor to the path of programmed death, it is necessary to artificially – for example, with the help of drugs – activate p53.
"In order to develop an effective treatment of malignant neoplasms, it is necessary, first of all, to study how the resistance of cancer cells to death can be overcome. To do this, in further studies, we plan to test how substances that activate the p53 protein act on tumors, or stimulate the work of mitochondria with a lack of oxygen. Perhaps this will become the basis for the development of new drugs against cancer," says Vladimir Gogvadze, Doctor of Biological Sciences, a leading researcher at the laboratory for the Study of apoptosis Mechanisms of the Faculty of Fundamental Medicine of Moscow State University.
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