Tag Archives: sodium dichloroacetate

Reprogramming of mitochondrial energy metabolism in malignant neoplasms

16.12.2015   Uncategorized   No comments

A. A. Kaplia1, L. V. Sorokina2, S. V. Khyzhnyak3

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: kaplya@biochem.kiev.ua;
2ESC “Institute of Biology”, Taras Shevchenko National University of Kyiv, Ukraine;
3National University of Life and Environmental Sciences of Ukraine, Kyiv

The novel ideas of fundamental role of mitochondria in the maintenance of viability of malignant cells have been reviewed. The modern state of research is considered in detail, including: mitochondrial control of the cellular redox state, sites of reactive oxygen species (ROS) production in inner mitochondrial membrane and antioxidant protection   systems. Specificities of the structural-functional mitochondrial remodelling in malignant tumors, the mechanisms of the energy metabolism reprogramming, enhancement of the ROS production and adaptation to the hypoxic conditions and metabolic stress are analyzed. The available data including our research on transplanted tumors indicate that cytotoxic action of sodium dichloroacetate (the inhibitor of pyruvate dehydrogenase kinase) depends on biological properties of tumors and intensity of structural-functional mitochondrial rearrangement. Dichloroacetate turned out to be effective for sarcoma 37, but not for Lewis lung carcinoma.

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Functional and dynamic state of inner mitochondrial membrane of sarcoma 37 in mice under administration of sodium dichloroacetate

20.07.2015   Uncategorized   No comments

S. V. Khyzhnyak1, L. V. Sorokina2, L. I. Stepanova3, A. A. Kaplia4

1National University of Life and Environmental Sciences of Ukraine, Kyiv;
e-mail: khs2014@ukr.net;
2R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv;
3ESC “Institute of Biology”, Taras Shevchenko National University of Kyiv, Ukraine;
4Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv

The activity of enzymes of the respiratory chain and structural-dynamic properties of the inner mitochondrial membrane (IMM) of sarcoma 37 (S37) in mice under  sodium dichloroacetate (SDA) administration in a daily dose of 86 mg/kg of body weight starting from the 2nd day after tumor transplantation were investigated. The dynamic and structural state of the IMM components was determined using the fluorescent probes. With S37 growth the intensification of glycolytic metabolism occurred on the background of suppressed functional capacity of mitochondrial respiratory chain enzymes. The changes of conformational properties of protein molecules and the increase of IMM lipid phase microviscosity were shown. The administration of SDA promotes the decrease of lactate content and the increase of pyruvate dehydrogenase activity in S37. This was accompanied by further suppression of the functional activity of the respiratory chain complexes and Н+-АТРase coupled with conformational modification of protein molecules and changes of the structural orderliness of the IMM lipid phase, possibly due to intensification of reactive oxygen species generation.

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