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Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

BACKGROUND: Triple-negative breast cancer accounts for approximately 15–20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of 1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trim...

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Autores principales: Ashourpour, Maryam, Mostafavi-Hosseini, Fatemeh, Amini, Mohsen, Saeedian Moghadam, Ebrahim, Kazerouni, Faranak, Arman, Seyed Yousef, Shahsavari, Zahra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607110/
https://www.ncbi.nlm.nih.gov/pubmed/34319030
http://dx.doi.org/10.31557/APJCP.2021.22.7.2079
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author Ashourpour, Maryam
Mostafavi-Hosseini, Fatemeh
Amini, Mohsen
Saeedian Moghadam, Ebrahim
Kazerouni, Faranak
Arman, Seyed Yousef
Shahsavari, Zahra
author_facet Ashourpour, Maryam
Mostafavi-Hosseini, Fatemeh
Amini, Mohsen
Saeedian Moghadam, Ebrahim
Kazerouni, Faranak
Arman, Seyed Yousef
Shahsavari, Zahra
author_sort Ashourpour, Maryam
collection PubMed
description BACKGROUND: Triple-negative breast cancer accounts for approximately 15–20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of 1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trimethoxyphenyl)- 1 H-Pyrazole were evaluated for their anticancer activity against MDA-MB-468, human triple negative breast cancer cell line. METHODS: The cytotoxic effects of Pyrazole derivatives on the growth of MDA-MB-468 and AGO1522 were determined using MTT assay. Annexin-V-FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The level of Reactive oxygen species (ROS) formation and caspase 3 activity were determined accordingly. RESULTS: Pyrazole derivatives induced a dose and time-dependent cell toxicity in MDA-MB-468 compared with untreated cells. The results showed that 3-(4-methoxyphenyl)-1-(p-tolyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-Pyrazole (3f) was the most active compound with IC(50) values 14.97 μM and 6.45 μM compared with Paclitaxel with IC(50) values 49.90 μM and 25.19 μM, after 24 and 48 hours, respectively. Upon treatment with 14.97 μM of 3f after 24 h, the compound induced cell cycle arrest in S phase. 3f provoked apoptosis was accompanied by the elevated level of ROS and increased caspase 3 activity in MDA-MB-468 cells compared with untreated cells. CONCLUSION: The overall results of the present study provided evidence for the cytotoxicity of compound 3f against MDA-MB-468 cells in comparison to reference standard, Paclitaxel. It proves that compound 3f can trigger apoptosis through ROS production and caspase 3 activation. These bring supportive data for future investigations that will lead to their use in cancer therapy.
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spelling pubmed-86071102021-11-26 Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468 Ashourpour, Maryam Mostafavi-Hosseini, Fatemeh Amini, Mohsen Saeedian Moghadam, Ebrahim Kazerouni, Faranak Arman, Seyed Yousef Shahsavari, Zahra Asian Pac J Cancer Prev Research Article BACKGROUND: Triple-negative breast cancer accounts for approximately 15–20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of 1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trimethoxyphenyl)- 1 H-Pyrazole were evaluated for their anticancer activity against MDA-MB-468, human triple negative breast cancer cell line. METHODS: The cytotoxic effects of Pyrazole derivatives on the growth of MDA-MB-468 and AGO1522 were determined using MTT assay. Annexin-V-FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The level of Reactive oxygen species (ROS) formation and caspase 3 activity were determined accordingly. RESULTS: Pyrazole derivatives induced a dose and time-dependent cell toxicity in MDA-MB-468 compared with untreated cells. The results showed that 3-(4-methoxyphenyl)-1-(p-tolyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-Pyrazole (3f) was the most active compound with IC(50) values 14.97 μM and 6.45 μM compared with Paclitaxel with IC(50) values 49.90 μM and 25.19 μM, after 24 and 48 hours, respectively. Upon treatment with 14.97 μM of 3f after 24 h, the compound induced cell cycle arrest in S phase. 3f provoked apoptosis was accompanied by the elevated level of ROS and increased caspase 3 activity in MDA-MB-468 cells compared with untreated cells. CONCLUSION: The overall results of the present study provided evidence for the cytotoxicity of compound 3f against MDA-MB-468 cells in comparison to reference standard, Paclitaxel. It proves that compound 3f can trigger apoptosis through ROS production and caspase 3 activation. These bring supportive data for future investigations that will lead to their use in cancer therapy. West Asia Organization for Cancer Prevention 2021-07 /pmc/articles/PMC8607110/ /pubmed/34319030 http://dx.doi.org/10.31557/APJCP.2021.22.7.2079 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ashourpour, Maryam
Mostafavi-Hosseini, Fatemeh
Amini, Mohsen
Saeedian Moghadam, Ebrahim
Kazerouni, Faranak
Arman, Seyed Yousef
Shahsavari, Zahra
Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468
title Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468
title_full Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468
title_fullStr Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468
title_full_unstemmed Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468
title_short Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468
title_sort pyrazole derivatives induce apoptosis via ros generation in the triple negative breast cancer cells, mda-mb-468
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607110/
https://www.ncbi.nlm.nih.gov/pubmed/34319030
http://dx.doi.org/10.31557/APJCP.2021.22.7.2079
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