Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.

An important approach in tumor therapy is combining substances with different action mechanisms aiming to enhance the antineoplastic effect, decrease the therapeutic dosage, and avoid resistance mechanisms. Moreover, evaluating compounds already approved for the treatment of non-neoplastic diseases...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Katharina Klose, Eva-Maria Packeiser, Petra Müller, José Luis Granados-Soler, Jan Torben Schille, Sandra Goericke-Pesch, Manfred Kietzmann, Hugo Murua Escobar, Ingo Nolte
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9996766d02f4e898c1f803b5286a128
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b9996766d02f4e898c1f803b5286a128
record_format	dspace
spelling	oai:doaj.org-article:b9996766d02f4e898c1f803b5286a1282021-12-02T20:06:08ZMetformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.1932-620310.1371/journal.pone.0257403https://doaj.org/article/b9996766d02f4e898c1f803b5286a1282021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257403https://doaj.org/toc/1932-6203An important approach in tumor therapy is combining substances with different action mechanisms aiming to enhance the antineoplastic effect, decrease the therapeutic dosage, and avoid resistance mechanisms. Moreover, evaluating compounds already approved for the treatment of non-neoplastic diseases is promising for new antineoplastic therapies. Sodium dichloroacetate (DCA) reactivates oxidative phosphorylation in the cancer cell mitochondria, reducing apoptosis resistance in cancer cells. Furthermore, metformin inhibits the proliferation of tumor cells and CD133+ cancer -stem-like cells. In the present study, we evaluated the independent and synergistic effect of metformin and DCA on the metabolic activity, cell proliferation, and apoptosis of a canine prostate adenocarcinoma (Adcarc1258) and a transitional cell carcinoma cell line (TCC1506) in comparison to a primary canine fibroblast culture. Determining metformin uptake in tumor cells was performed by quantitative HPLC. Depending on the dosage, metformin as a single agent inhibited the metabolic activity and cell proliferation of the tumor cells, showing only minor effects on the fibroblasts. Furthermore, 1 mM metformin increased apoptosis over 96 h in the tumor cell lines but not in fibroblasts. Additionally, metformin uptake into the tumor cells in vitro was measurable by quantitative HPLC. Synergistic effects for the combination therapy were observed in both neoplastic cell lines as well as in the fibroblasts. Based on these results, metformin might be a promising therapeutic agent for canine urogenital tumors. Further studies on kinetics, toxicology, bioavailability, and application of metformin in dogs are necessary.Katharina KloseEva-Maria PackeiserPetra MüllerJosé Luis Granados-SolerJan Torben SchilleSandra Goericke-PeschManfred KietzmannHugo Murua EscobarIngo NoltePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257403 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katharina Klose Eva-Maria Packeiser Petra Müller José Luis Granados-Soler Jan Torben Schille Sandra Goericke-Pesch Manfred Kietzmann Hugo Murua Escobar Ingo Nolte Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
description	An important approach in tumor therapy is combining substances with different action mechanisms aiming to enhance the antineoplastic effect, decrease the therapeutic dosage, and avoid resistance mechanisms. Moreover, evaluating compounds already approved for the treatment of non-neoplastic diseases is promising for new antineoplastic therapies. Sodium dichloroacetate (DCA) reactivates oxidative phosphorylation in the cancer cell mitochondria, reducing apoptosis resistance in cancer cells. Furthermore, metformin inhibits the proliferation of tumor cells and CD133+ cancer -stem-like cells. In the present study, we evaluated the independent and synergistic effect of metformin and DCA on the metabolic activity, cell proliferation, and apoptosis of a canine prostate adenocarcinoma (Adcarc1258) and a transitional cell carcinoma cell line (TCC1506) in comparison to a primary canine fibroblast culture. Determining metformin uptake in tumor cells was performed by quantitative HPLC. Depending on the dosage, metformin as a single agent inhibited the metabolic activity and cell proliferation of the tumor cells, showing only minor effects on the fibroblasts. Furthermore, 1 mM metformin increased apoptosis over 96 h in the tumor cell lines but not in fibroblasts. Additionally, metformin uptake into the tumor cells in vitro was measurable by quantitative HPLC. Synergistic effects for the combination therapy were observed in both neoplastic cell lines as well as in the fibroblasts. Based on these results, metformin might be a promising therapeutic agent for canine urogenital tumors. Further studies on kinetics, toxicology, bioavailability, and application of metformin in dogs are necessary.
format	article
author	Katharina Klose Eva-Maria Packeiser Petra Müller José Luis Granados-Soler Jan Torben Schille Sandra Goericke-Pesch Manfred Kietzmann Hugo Murua Escobar Ingo Nolte
author_facet	Katharina Klose Eva-Maria Packeiser Petra Müller José Luis Granados-Soler Jan Torben Schille Sandra Goericke-Pesch Manfred Kietzmann Hugo Murua Escobar Ingo Nolte
author_sort	Katharina Klose
title	Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
title_short	Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
title_full	Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
title_fullStr	Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
title_full_unstemmed	Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
title_sort	metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b9996766d02f4e898c1f803b5286a128
work_keys_str_mv	AT katharinaklose metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT evamariapackeiser metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT petramuller metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT joseluisgranadossoler metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT jantorbenschille metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT sandragoerickepesch metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT manfredkietzmann metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT hugomuruaescobar metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline AT ingonolte metforminandsodiumdichloroacetateeffectsonproliferationapoptosisandmetabolicactivitytestedaloneandincombinationinacanineprostateandabladdercancercellline
_version_	1718375446313172992

Metformin and sodium dichloroacetate effects on proliferation, apoptosis, and metabolic activity tested alone and in combination in a canine prostate and a bladder cancer cell line.

Ejemplares similares