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Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro

Breast cancer is the second leading cause of death among women globally. The existing treatment options for breast cancer are largely associated with severe toxicities, and lower efficacies. Therefore, there is an urgent need for the development of non-toxic effective drugs against breast cancer. Fo...

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Autores principales: Badran, Adnan, tul-Wahab, Atia, Zafar, Humaira, Mohammad, Nayab, Imad, Rehan, Ashfaq Khan, Mariam, Baydoun, Elias, Choudhary, M. Iqbal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398703/
https://www.ncbi.nlm.nih.gov/pubmed/32746451
http://dx.doi.org/10.1371/journal.pone.0235676
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author Badran, Adnan
tul-Wahab, Atia
Zafar, Humaira
Mohammad, Nayab
Imad, Rehan
Ashfaq Khan, Mariam
Baydoun, Elias
Choudhary, M. Iqbal
author_facet Badran, Adnan
tul-Wahab, Atia
Zafar, Humaira
Mohammad, Nayab
Imad, Rehan
Ashfaq Khan, Mariam
Baydoun, Elias
Choudhary, M. Iqbal
author_sort Badran, Adnan
collection PubMed
description Breast cancer is the second leading cause of death among women globally. The existing treatment options for breast cancer are largely associated with severe toxicities, and lower efficacies. Therefore, there is an urgent need for the development of non-toxic effective drugs against breast cancer. For this purpose, drug repositioning strategy was used to evaluate the anti-cancer potential of a library of heterocyclic drugs. The major advantage of drug repurposing is that the pharmacokinetic, pharmacodynamic, and toxicity profiles of drugs are well documented. In the current study, we screened 97 drugs of different chemical classes, and among them aripiprazole, an antipsychotic drug, was found to be sufficiently active against breast cancer cell line MCF-7. Aripiprazole showed a cytotoxicity (IC(50) = 12.1 ± 0.40 μM) to MCF-7 cells, comparable to the standard anticancer drug doxorubicin (IC(50) = 1.25 ± 0.34 μM). Aripiprazole was also found to be active against other cancer cell lines, including MDA-MB-231 (IC(50) = 19.83 ± 0.27 μM), AU565 (IC(50) = 18.02 ± 0.44 μM), and BT-474 (IC(50) = 36.42 ± 0.12 μM). Aripiprazole significantly inhibited the cell cycle progression at subG(0)G(1) phase, and enhanced apoptosis in MCF-7 breast cancer cells. The drug was also able to significantly increase the nuclear condensation, and modulated the expression of certain genes involved in breast cancer, such as caspases 3, and 9, BAK-1, C-MYC, BCL2L1, BCL-10, and BCL-2. Further studies are needed to explore the effect of aripiprazole on intrinsic and extrinsic pathways of apoptosis in cancer cells.
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spelling pubmed-73987032020-08-14 Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro Badran, Adnan tul-Wahab, Atia Zafar, Humaira Mohammad, Nayab Imad, Rehan Ashfaq Khan, Mariam Baydoun, Elias Choudhary, M. Iqbal PLoS One Research Article Breast cancer is the second leading cause of death among women globally. The existing treatment options for breast cancer are largely associated with severe toxicities, and lower efficacies. Therefore, there is an urgent need for the development of non-toxic effective drugs against breast cancer. For this purpose, drug repositioning strategy was used to evaluate the anti-cancer potential of a library of heterocyclic drugs. The major advantage of drug repurposing is that the pharmacokinetic, pharmacodynamic, and toxicity profiles of drugs are well documented. In the current study, we screened 97 drugs of different chemical classes, and among them aripiprazole, an antipsychotic drug, was found to be sufficiently active against breast cancer cell line MCF-7. Aripiprazole showed a cytotoxicity (IC(50) = 12.1 ± 0.40 μM) to MCF-7 cells, comparable to the standard anticancer drug doxorubicin (IC(50) = 1.25 ± 0.34 μM). Aripiprazole was also found to be active against other cancer cell lines, including MDA-MB-231 (IC(50) = 19.83 ± 0.27 μM), AU565 (IC(50) = 18.02 ± 0.44 μM), and BT-474 (IC(50) = 36.42 ± 0.12 μM). Aripiprazole significantly inhibited the cell cycle progression at subG(0)G(1) phase, and enhanced apoptosis in MCF-7 breast cancer cells. The drug was also able to significantly increase the nuclear condensation, and modulated the expression of certain genes involved in breast cancer, such as caspases 3, and 9, BAK-1, C-MYC, BCL2L1, BCL-10, and BCL-2. Further studies are needed to explore the effect of aripiprazole on intrinsic and extrinsic pathways of apoptosis in cancer cells. Public Library of Science 2020-08-03 /pmc/articles/PMC7398703/ /pubmed/32746451 http://dx.doi.org/10.1371/journal.pone.0235676 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Badran, Adnan
tul-Wahab, Atia
Zafar, Humaira
Mohammad, Nayab
Imad, Rehan
Ashfaq Khan, Mariam
Baydoun, Elias
Choudhary, M. Iqbal
Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro
title Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro
title_full Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro
title_fullStr Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro
title_full_unstemmed Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro
title_short Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro
title_sort antipsychotics drug aripiprazole as a lead against breast cancer cell line (mcf-7) in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398703/
https://www.ncbi.nlm.nih.gov/pubmed/32746451
http://dx.doi.org/10.1371/journal.pone.0235676
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