Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma

Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma

Significant variability of anticancer efficacy of dichloroacetate (DCA) stimulated an active search for the agents capable to enhance it antitumor action. Therefore, the aim of this work is the study of capability of aconitine-containing antiangiogenic agent BC1 to enhance anticancer activity of DCA...

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Видавець:Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
Дата:2015
Автори: Pyaskovskaya, O.N., Boychuk, I.V., Fedorchuk, A.G., Kolesnik, D.L., Dasyukevich, O.I., Solyanik, G.I.
Формат: Стаття
Мова:English
Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2015
Назва видання:Experimental Oncology
Теми:
Original contributions
Онлайн доступ:http://dspace.nbuv.gov.ua/handle/123456789/145487
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Цитувати:Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma / O.N. Pyaskovskaya, I.V. Boychuk, A.G. Fedorchuk, D.L. Kolesnik, O.I. Dasyukevich, G.I. Solyanik // Experimental Oncology. — 2015. — Т. 37, № 3. — С. 192-196. — Бібліогр.: 27 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
id irk-123456789-145487
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spelling irk-123456789-1454872019-01-23T01:23:48Z Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma Pyaskovskaya, O.N. Boychuk, I.V. Fedorchuk, A.G. Kolesnik, D.L. Dasyukevich, O.I. Solyanik, G.I. Original contributions Significant variability of anticancer efficacy of dichloroacetate (DCA) stimulated an active search for the agents capable to enhance it antitumor action. Therefore, the aim of this work is the study of capability of aconitine-containing antiangiogenic agent BC1 to enhance anticancer activity of DCA against Ehrlich carcinoma. Materials and Methods: DCA (total dose was 1.3 g/kg of b.w.) and BC1 (total dose was 0.9 mg/kg of b.w.) were administered per os starting from the 2nd and 3rd days, respectively (8 admini­strations for each agent). Antitumor efficacy of agents was estimated. Lactate level, LDH activity and the state of mitochondrial electron transport chain in tumor cells as well as phagocytic activity and reactive oxygen species (ROS) production of tumor-associated macrophages (TAM) were studied. Results: Combined administration of DCA and ВС1 resulted in 89.8% tumor growth inhibition (p < 0.001), what is by 22.5% (p < 0.05) higher that that of DCA alone. This combined treatment was accompanied with a decrease of lactate level in tumor tissue by 30% (p < 0.05) and significant elevation of LDH activity by 70% (p < 0.01). Increased level of NO-Fe-S clusters and 2-fold reduction of Fe-S cluster content were revealed in tumor tissue of mice after DCA and BC1 administration. It was shown that combined therapy did not effect TAM quantity and their phagocytic activity but stimulated ROS production by TAMs by 78% (p < 0.05) compared to this index in control animals. Conclusion: Antiangiogenic agent ВС1 in combination with DCA considerably enhances antitumor activity of DCA via significant decrease of Fe-S-containing protein level resulted from substantial elevation of nitrosylation of these proteins. Key Words: Ehrlich carcinoma, dichloroacetate, aconitine-containing agent, tumor-associated macrophages, mitochondrial electron transport chain. 2015 Article Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma / O.N. Pyaskovskaya, I.V. Boychuk, A.G. Fedorchuk, D.L. Kolesnik, O.I. Dasyukevich, G.I. Solyanik // Experimental Oncology. — 2015. — Т. 37, № 3. — С. 192-196. — Бібліогр.: 27 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/145487 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Pyaskovskaya, O.N.
Boychuk, I.V.
Fedorchuk, A.G.
Kolesnik, D.L.
Dasyukevich, O.I.
Solyanik, G.I.
Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma
Experimental Oncology
description Significant variability of anticancer efficacy of dichloroacetate (DCA) stimulated an active search for the agents capable to enhance it antitumor action. Therefore, the aim of this work is the study of capability of aconitine-containing antiangiogenic agent BC1 to enhance anticancer activity of DCA against Ehrlich carcinoma. Materials and Methods: DCA (total dose was 1.3 g/kg of b.w.) and BC1 (total dose was 0.9 mg/kg of b.w.) were administered per os starting from the 2nd and 3rd days, respectively (8 admini­strations for each agent). Antitumor efficacy of agents was estimated. Lactate level, LDH activity and the state of mitochondrial electron transport chain in tumor cells as well as phagocytic activity and reactive oxygen species (ROS) production of tumor-associated macrophages (TAM) were studied. Results: Combined administration of DCA and ВС1 resulted in 89.8% tumor growth inhibition (p < 0.001), what is by 22.5% (p < 0.05) higher that that of DCA alone. This combined treatment was accompanied with a decrease of lactate level in tumor tissue by 30% (p < 0.05) and significant elevation of LDH activity by 70% (p < 0.01). Increased level of NO-Fe-S clusters and 2-fold reduction of Fe-S cluster content were revealed in tumor tissue of mice after DCA and BC1 administration. It was shown that combined therapy did not effect TAM quantity and their phagocytic activity but stimulated ROS production by TAMs by 78% (p < 0.05) compared to this index in control animals. Conclusion: Antiangiogenic agent ВС1 in combination with DCA considerably enhances antitumor activity of DCA via significant decrease of Fe-S-containing protein level resulted from substantial elevation of nitrosylation of these proteins. Key Words: Ehrlich carcinoma, dichloroacetate, aconitine-containing agent, tumor-associated macrophages, mitochondrial electron transport chain.
format Article
author Pyaskovskaya, O.N.
Boychuk, I.V.
Fedorchuk, A.G.
Kolesnik, D.L.
Dasyukevich, O.I.
Solyanik, G.I.
author_facet Pyaskovskaya, O.N.
Boychuk, I.V.
Fedorchuk, A.G.
Kolesnik, D.L.
Dasyukevich, O.I.
Solyanik, G.I.
author_sort Pyaskovskaya, O.N.
title Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma
title_short Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma
title_full Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma
title_fullStr Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma
title_full_unstemmed Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma
title_sort aconitine-containing agent enhances antitumor activity of dichloroacetate against ehrlich carcinoma
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2015
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/145487
citation_txt Aconitine-containing agent enhances antitumor activity of dichloroacetate against Ehrlich carcinoma / O.N. Pyaskovskaya, I.V. Boychuk, A.G. Fedorchuk, D.L. Kolesnik, O.I. Dasyukevich, G.I. Solyanik // Experimental Oncology. — 2015. — Т. 37, № 3. — С. 192-196. — Бібліогр.: 27 назв. — англ.
series Experimental Oncology
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first_indexed 2023-05-20T17:22:17Z
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