Laura Korsakova1, Jan Aleksander Krasko2, Edgaras Stankevicius1. 1. Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania; martinkutelaura@gmail.com. 2. National Cancer Institute, Vilnius, Lithuania.
Abstract
BACKGROUND/AIM: We investigated the hypothesis that dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, and metformin (MET), an antidiabetic agent and complex I inhibitor, have synergistic cytotoxic effects in glioblastoma cells in vitro and in vivo. MATERIALS AND METHODS: We performed dose response experiments and combination index calculation. Apoptotic and necrotic cells were estimated by flow cytometry. Cell metabolism was evaluated by Seahorse analysis and lactate export. Overall survival and tumor volume growth experiments were performed in C57BL/6 mice GL-261 allograft model. RESULTS: DCA and MET showed dose-dependent cytotoxicity and synergistic effects. DCA alleviated the increase in lactate production induced by MET. Seahorse analysis showed that DCA treatment results in increased oxygen consumption rate, which is decreased by MET. DCA and MET significantly inhibited tumor growth and increased overall survival in mice. CONCLUSION: Compounds targeting tumor cell metabolism could become potential treatment options for glioblastoma multiforme. Copyright
BACKGROUND/AIM: We investigated the hypothesis that dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, and metformin (MET), an antidiabetic agent and complex I inhibitor, have synergistic cytotoxic effects in glioblastoma cells in vitro and in vivo. MATERIALS AND METHODS: We performed dose response experiments and combination index calculation. Apoptotic and necrotic cells were estimated by flow cytometry. Cell metabolism was evaluated by Seahorse analysis and lactate export. Overall survival and tumor volume growth experiments were performed in C57BL/6 mice GL-261 allograft model. RESULTS:DCA and MET showed dose-dependent cytotoxicity and synergistic effects. DCA alleviated the increase in lactate production induced by MET. Seahorse analysis showed that DCA treatment results in increased oxygen consumption rate, which is decreased by MET. DCA and MET significantly inhibited tumor growth and increased overall survival in mice. CONCLUSION: Compounds targeting tumor cell metabolism could become potential treatment options for glioblastoma multiforme. Copyright
Authors: Thomas N Seyfried; Roberto Flores; Angela M Poff; Dominic P D'Agostino; Purna Mukherjee Journal: Cancer Lett Date: 2014-07-25 Impact factor: 8.679
Authors: Issam Ben Sahra; Yannick Le Marchand-Brustel; Jean-François Tanti; Frédéric Bost Journal: Mol Cancer Ther Date: 2010-05-04 Impact factor: 6.261
Authors: Ghassan M Saed; Nicole M Fletcher; Zhong L Jiang; Husam M Abu-Soud; Michael P Diamond Journal: Reprod Sci Date: 2011-06-23 Impact factor: 3.060
Authors: Claire M Larrieu; Simon Storevik; Joris Guyon; Antonio C Pagano Zottola; Cyrielle L Bouchez; Marie-Alix Derieppe; Tuan Zea Tan; Hrvoje Miletic; James Lorens; Karl Johan Tronstad; Thomas Daubon; Gro Vatne Røsland Journal: Cancers (Basel) Date: 2022-08-02 Impact factor: 6.575