aconitine and Carcinoma--Ehrlich-Tumor

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.. 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 2(nd) and 3(rd) days, respectively (8 admini-strations 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.. 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.. 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.

Topics: Aconitine; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Dichloroacetic Acid; Disease Models, Animal; Drug Synergism; Humans; Lactate Dehydrogenases; Lactic Acid; Mice; Nitric Oxide; Reactive Oxygen Species; Tumor Burden; Xenograft Model Antitumor Assays

To study anticancer activity of conitine-containing agent BC1 in vivo.. BC1 water solution was administered per os to mice bearing ascite or solid form of Ehrlich's carcinoma. Anticancer effect of BC1 administered per os was evaluated by the indexes of tumor growth inhibition and average life span of experimental animals.. BC1 didn't show anticancer activity in the case of ascite form of Ehrlich's carcinoma. At the same time treatment with BC1 resulted in 77.3% growth inhibition of solid form of Ehrlich's carcinoma (p < 0.05).. BC1 is active in vivo against tumor with angiogenesis-dependent growth.

Topics: Aconitine; Aconitum; Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Female; Mice; Phytotherapy; Plant Preparations