L.Y. Grivtsova, PhD in medical science, PhD in biology science, Head of Laboratory Medicine Department, Head of Clinical Immunology Laboratory of A.F. Tsyba MRSC, a branch of the Federal State Budgetary Institution “NMRC of Radiology” of the Ministry of Health of the Russian Federation

Over the last ten years, the ideas of molecular oncology about the energy metabolism of malignant cells have changed dramatically, and new molecular mechanisms in the cascade pathways of cancer bioenergetics are being searched for. Numerous data show that the emergence and development of tumors are closely related to the metabolism of iron ions (Fe). Inorganic substrates, namely iron ions involved in the metabolic processes of the tumor cell, have received limited attention in the world literature to date.

Our research group has put forward and is developing the concept of «Energy metaplasia of cancer cells», i.e. acquisition of an additional autotrophic way of energy production (respiratory reactions involving iron ions) in the process of oncogenesis. Proof of the hypothesis opens prospects for explaining some issues of oncogenesis and a new approach to the treatment of cancer.

The aim of the study: to investigate and obtain evidence for the existence of respiratory (chemosynthetic) reactions involving iron ions as a way to obtain energy in cancer cells.

The studies were conducted on the basis of the «Center of Cell Technologies», Samara city, Russia, under the guidance of specialists from A.F. Tsyba MRSC, Obninsk city, Russia. All experiments were conducted in vitro using HeLa cell line (cervical carcinoma) and human mesenchymal stromal cell line (MSC) culture as a control. The proof-of-concept study was carried out in 3 stages. The 1st stage was analytical review, the 2nd stage - study of energy metabolism by extracellular flux analysis on the SeaHorseXFp apparatus (USA), the 3rd stage - bioinformatic study on search in the human genome for homolog genes responsible for chemosynthetic reactions using blastp and exonerate programs.

As a result of the analytical review of works on the evolution of the way of energy production by plant and animal cells, a possible chemosynthetic reaction in cancer cells - oxidation of iron ions (Fe+2 - Fe+3+E) was revealed. As a result of 50 performed protocols on SeaHorseXFp cell metabolism analyzer we found suppression of two classical pathways of energy production - oxidative phosphorylation (by 54,2%) and glycolysis (by 85,4%) in malignant HeLa culture in contrast to normal index in MSC cell culture. As a result of bioinformatic study, 6 proteins and 11 domains related to iron metabolism were found in the human genome, which are highly similar in sequence to the genes responsible for chemosynthetic reactions involving iron ions in iron bacteria.

Thus, respiratory chemosynthetic reactions involving iron ions are possible in malignant cells, which allows the cancer cell to change its energy phenotype and acquire an additional autotrophic way of energy production, allowing it to acquire the properties of uncontrolled growth and metastatic spread. This molecular cascade requires additional study and is of interest as a target for the development of targeted antitumor drugs.