The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo
| Autor: | Marta M. Alonso, Milda Juknevičienė, Ingrida Balnytė, Angelija Valančiūtė, Eligija Damanskienė, Donatas Stakišaitis |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Neoplasms drug therapy Dichloroacetic acid pharmacology Sodium dichloroacetate Review Mitochondrion Pharmacology lcsh:RC254-282 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Gender differences cancer Medicine preclinical research Cancer business.industry Sodium Dichloroacetate sodium dichloroacetate lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Pyruvate dehydrogenase complex medicine.disease 3. Good health Pyruvate dehydrogenase deficiency 030104 developmental biology Oncology chemistry Preclinical research gender differences 030220 oncology & carcinogenesis Cancer cell business 616-006.6 [udc] |
| Zdroj: | Cancers, Vol 11, Iss 8, p 1210 (2019) Cancers, Basel : MDPI, 2019, vol. 11, no. 8, 1210, p. 1-28 Cancers Dadun. Depósito Académico Digital de la Universidad de Navarra instname |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers11081210 |
| Popis: | Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in cancer cells’ mitochondria. Inhibition of pyruvate dehydrogenase kinases by DCA keeps the pyruvate dehydrogenase complex in the active form, resulting in decreased lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA’s effects on the cell pyruvate dehydrogenase deficiency, pyruvate mitochondrial oxidative phosphorylation, reactive oxygen species generation, and the Na+−K+−2Cl− cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human cancer xenografts in vivo in male and female animals. Preclinical cancer researchers report the synergistic effects of DCA combined with different drugs on cancer by reversing resistance to chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA’s effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad hormone dependency could be relevant for individualized therapy approaches so that gender-related differences in treatment response and safety can be proposed. |
| Databáze: | OpenAIRE |
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