Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells

Sushmita Chatterjee, Nirmal Thaker, Abhijit DeMolecular Functional Imaging Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, IndiaAbstract: Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various cancer...

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Autores principales:	Chatterjee S, Thaker N, De A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5e9939871a03459281944a22ccc8a48e
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spelling	oai:doaj.org-article:5e9939871a03459281944a22ccc8a48e2021-12-02T01:26:47ZCombined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells1179-1314https://doaj.org/article/5e9939871a03459281944a22ccc8a48e2015-08-01T00:00:00Zhttp://www.dovepress.com/combined-2-deoxy-glucose-and-metformin-improves-therapeutic-efficacy-o-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Sushmita Chatterjee, Nirmal Thaker, Abhijit DeMolecular Functional Imaging Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, IndiaAbstract: Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC) cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5) protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated 131I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy) Cobalt60 radiation shows significant radiosensitization effect (P=0.0002). In cells treated with the combination therapy, increased γH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS) was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019) by 50 µ Ci 131I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP) content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS-mediated-targeted radioiodine therapy, which otherwise may have lacked efficacy.Keywords: sodium-iodide symporter, 2-DG, 131I, radiosensitizersChatterjee SThaker NDe ADove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2015, Iss default, Pp 251-265 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chatterjee S Thaker N De A Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells
description	Sushmita Chatterjee, Nirmal Thaker, Abhijit DeMolecular Functional Imaging Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, IndiaAbstract: Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC) cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5) protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated 131I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy) Cobalt60 radiation shows significant radiosensitization effect (P=0.0002). In cells treated with the combination therapy, increased γH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS) was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019) by 50 µ Ci 131I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP) content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS-mediated-targeted radioiodine therapy, which otherwise may have lacked efficacy.Keywords: sodium-iodide symporter, 2-DG, 131I, radiosensitizers
format	article
author	Chatterjee S Thaker N De A
author_facet	Chatterjee S Thaker N De A
author_sort	Chatterjee S
title	Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells
title_short	Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells
title_full	Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells
title_fullStr	Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells
title_full_unstemmed	Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells
title_sort	combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/5e9939871a03459281944a22ccc8a48e
work_keys_str_mv	AT chatterjees combined2deoxyglucoseandmetforminimprovestherapeuticefficacyofsodiumiodidesymportermediatedtargetedradioiodinetherapyinbreastcancercells AT thakern combined2deoxyglucoseandmetforminimprovestherapeuticefficacyofsodiumiodidesymportermediatedtargetedradioiodinetherapyinbreastcancercells AT dea combined2deoxyglucoseandmetforminimprovestherapeuticefficacyofsodiumiodidesymportermediatedtargetedradioiodinetherapyinbreastcancercells
_version_	1718403075253731328

Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells

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