author_facet Shafiei‐Irannejad, Vahid
Samadi, Nasser
Yousefi, Bahman
Salehi, Roya
Velaei, Kobra
Zarghami, Nosratollah
Shafiei‐Irannejad, Vahid
Samadi, Nasser
Yousefi, Bahman
Salehi, Roya
Velaei, Kobra
Zarghami, Nosratollah
author Shafiei‐Irannejad, Vahid
Samadi, Nasser
Yousefi, Bahman
Salehi, Roya
Velaei, Kobra
Zarghami, Nosratollah
spellingShingle Shafiei‐Irannejad, Vahid
Samadi, Nasser
Yousefi, Bahman
Salehi, Roya
Velaei, Kobra
Zarghami, Nosratollah
Chemical Biology & Drug Design
Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
Molecular Medicine
Biochemistry
Drug Discovery
Pharmacology
Organic Chemistry
author_sort shafiei‐irannejad, vahid
spelling Shafiei‐Irannejad, Vahid Samadi, Nasser Yousefi, Bahman Salehi, Roya Velaei, Kobra Zarghami, Nosratollah 1747-0277 1747-0285 Wiley Molecular Medicine Biochemistry Drug Discovery Pharmacology Organic Chemistry http://dx.doi.org/10.1111/cbdd.13078 <jats:p>Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side‐effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX)‐resistant breast cancer (MCF‐7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P‐gp mRNA/protein expression levels following treatment with metformin were determined using real‐time polymerase chain reaction and Western blot analysis, respectively. Intracellular rhodamine 123 accumulation assay was performed to evaluate the P‐gp function. Cellular ATP content was determined using ATP assay kit. The effect of metformin on DOX‐induced apoptosis was evaluated by annexin V/FITC assay. Exposure to metformin considerably enhanced the cytotoxicity of DOX. Metformin had no substantial effect on P‐gp expression, while the activity of P‐gp and intracellular ATP content decreased with metformin treatment in a dose‐dependent manner. Furthermore, metformin significantly increased the DOX‐induced apoptosis. These results indicate that metformin could reverse MDR in breast cancer cells by reducing P‐gp activity. Therefore, metformin can be suggested as a potent adjuvant in breast cancer chemotherapy.</jats:p> Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells Chemical Biology & Drug Design
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title Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_unstemmed Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_full Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_fullStr Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_full_unstemmed Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_short Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_sort metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in p‐gp‐overexpressing mcf‐7 cells
topic Molecular Medicine
Biochemistry
Drug Discovery
Pharmacology
Organic Chemistry
url http://dx.doi.org/10.1111/cbdd.13078
publishDate 2018
physical 269-276
description <jats:p>Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side‐effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX)‐resistant breast cancer (MCF‐7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P‐gp mRNA/protein expression levels following treatment with metformin were determined using real‐time polymerase chain reaction and Western blot analysis, respectively. Intracellular rhodamine 123 accumulation assay was performed to evaluate the P‐gp function. Cellular ATP content was determined using ATP assay kit. The effect of metformin on DOX‐induced apoptosis was evaluated by annexin V/FITC assay. Exposure to metformin considerably enhanced the cytotoxicity of DOX. Metformin had no substantial effect on P‐gp expression, while the activity of P‐gp and intracellular ATP content decreased with metformin treatment in a dose‐dependent manner. Furthermore, metformin significantly increased the DOX‐induced apoptosis. These results indicate that metformin could reverse MDR in breast cancer cells by reducing P‐gp activity. Therefore, metformin can be suggested as a potent adjuvant in breast cancer chemotherapy.</jats:p>
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author Shafiei‐Irannejad, Vahid, Samadi, Nasser, Yousefi, Bahman, Salehi, Roya, Velaei, Kobra, Zarghami, Nosratollah
author_facet Shafiei‐Irannejad, Vahid, Samadi, Nasser, Yousefi, Bahman, Salehi, Roya, Velaei, Kobra, Zarghami, Nosratollah, Shafiei‐Irannejad, Vahid, Samadi, Nasser, Yousefi, Bahman, Salehi, Roya, Velaei, Kobra, Zarghami, Nosratollah
author_sort shafiei‐irannejad, vahid
container_issue 1
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description <jats:p>Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side‐effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX)‐resistant breast cancer (MCF‐7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P‐gp mRNA/protein expression levels following treatment with metformin were determined using real‐time polymerase chain reaction and Western blot analysis, respectively. Intracellular rhodamine 123 accumulation assay was performed to evaluate the P‐gp function. Cellular ATP content was determined using ATP assay kit. The effect of metformin on DOX‐induced apoptosis was evaluated by annexin V/FITC assay. Exposure to metformin considerably enhanced the cytotoxicity of DOX. Metformin had no substantial effect on P‐gp expression, while the activity of P‐gp and intracellular ATP content decreased with metformin treatment in a dose‐dependent manner. Furthermore, metformin significantly increased the DOX‐induced apoptosis. These results indicate that metformin could reverse MDR in breast cancer cells by reducing P‐gp activity. Therefore, metformin can be suggested as a potent adjuvant in breast cancer chemotherapy.</jats:p>
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spelling Shafiei‐Irannejad, Vahid Samadi, Nasser Yousefi, Bahman Salehi, Roya Velaei, Kobra Zarghami, Nosratollah 1747-0277 1747-0285 Wiley Molecular Medicine Biochemistry Drug Discovery Pharmacology Organic Chemistry http://dx.doi.org/10.1111/cbdd.13078 <jats:p>Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side‐effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX)‐resistant breast cancer (MCF‐7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P‐gp mRNA/protein expression levels following treatment with metformin were determined using real‐time polymerase chain reaction and Western blot analysis, respectively. Intracellular rhodamine 123 accumulation assay was performed to evaluate the P‐gp function. Cellular ATP content was determined using ATP assay kit. The effect of metformin on DOX‐induced apoptosis was evaluated by annexin V/FITC assay. Exposure to metformin considerably enhanced the cytotoxicity of DOX. Metformin had no substantial effect on P‐gp expression, while the activity of P‐gp and intracellular ATP content decreased with metformin treatment in a dose‐dependent manner. Furthermore, metformin significantly increased the DOX‐induced apoptosis. These results indicate that metformin could reverse MDR in breast cancer cells by reducing P‐gp activity. Therefore, metformin can be suggested as a potent adjuvant in breast cancer chemotherapy.</jats:p> Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells Chemical Biology & Drug Design
spellingShingle Shafiei‐Irannejad, Vahid, Samadi, Nasser, Yousefi, Bahman, Salehi, Roya, Velaei, Kobra, Zarghami, Nosratollah, Chemical Biology & Drug Design, Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells, Molecular Medicine, Biochemistry, Drug Discovery, Pharmacology, Organic Chemistry
title Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_full Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_fullStr Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_full_unstemmed Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_short Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
title_sort metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in p‐gp‐overexpressing mcf‐7 cells
title_unstemmed Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
topic Molecular Medicine, Biochemistry, Drug Discovery, Pharmacology, Organic Chemistry
url http://dx.doi.org/10.1111/cbdd.13078