Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer Cells
Triple-negative breast cancer (TNBC), the most aggressive subtype, does not respond to targeted therapy due to the lack of hormone receptors. There is an urgent need for alternative therapies, including natural product-based anti-cancer drugs, at lower cost. We investigated the impact of a Calligonu...
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Series: | Journal of Evidence-Based Integrative Medicine |
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doaj-95af4562276b4d5eb2cf8f330a35466d2020-12-12T01:33:27ZengSAGE PublishingJournal of Evidence-Based Integrative Medicine2515-690X2020-12-012510.1177/2515690X20978391Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer CellsZeyad Alehaideb PhD0Saleh AlGhamdi PhD1Wesam Bin Yahya BSc2Hamad Al-Eidi BSc3Mashael Alharbi MSc4Monira Alaujan MSc5Abeer Albaz MSc6Muruj Tukruni BSc7Atef Nehdi PhD8Maha-Hamadien Abdulla PhD9Sabine Matou-Nasri PhD10 King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia Clinical Research Department, Research Center, King Fahad Medical City, Riyadh, Saudi Arabia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia Department of Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia Department of Surgery, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaTriple-negative breast cancer (TNBC), the most aggressive subtype, does not respond to targeted therapy due to the lack of hormone receptors. There is an urgent need for alternative therapies, including natural product-based anti-cancer drugs, at lower cost. We investigated the impact of a Calligonum comosum L’Hér. methanolic extract (CcME) on the TNBC MDA-MB-231 cell line proliferation and related cell death mechanisms performing cell viability and cytotoxicity assays, flow cytometry to detect apoptosis and cell cycle analysis. The apoptosis-related protein array and cellular reactive oxygen species (ROS) assay were also carried out. We showed that the CcME inhibited the TNBC cell viability, in a dose-dependent manner, with low cytotoxic effects. The CcME-treated TNBC cells underwent apoptosis, associated with a concomitant increase of apoptosis-related protein expression, including cytochrome c, cleaved caspase-3, cyclin-dependent kinase inhibitor p21, and the anti-oxidant enzyme catalase, compared with the untreated cells. The CcME also enhanced the mitochondrial transition pore opening activity and induced G 0 /G 1 cell growth arrest, which confirmed the cytochrome c release and the increase of the p21 expression detected in the CcME-treated TNBC cells. The CcME-treated TNBC cells resulted in intracellular ROS production, which, when blocked with a ROS scavenger, did not reduce the CcME-induced apoptosis. In conclusion, CcME exerts anti-proliferative effects against TNBC cells through the induction of apoptosis and cell growth arrest. In vivo studies are justified to verify the CcME anti-proliferative activities and to investigate any potential anti-metastatic activities of CcME against TNBC development and progression.https://doi.org/10.1177/2515690X20978391 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zeyad Alehaideb PhD Saleh AlGhamdi PhD Wesam Bin Yahya BSc Hamad Al-Eidi BSc Mashael Alharbi MSc Monira Alaujan MSc Abeer Albaz MSc Muruj Tukruni BSc Atef Nehdi PhD Maha-Hamadien Abdulla PhD Sabine Matou-Nasri PhD |
spellingShingle |
Zeyad Alehaideb PhD Saleh AlGhamdi PhD Wesam Bin Yahya BSc Hamad Al-Eidi BSc Mashael Alharbi MSc Monira Alaujan MSc Abeer Albaz MSc Muruj Tukruni BSc Atef Nehdi PhD Maha-Hamadien Abdulla PhD Sabine Matou-Nasri PhD Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer Cells Journal of Evidence-Based Integrative Medicine |
author_facet |
Zeyad Alehaideb PhD Saleh AlGhamdi PhD Wesam Bin Yahya BSc Hamad Al-Eidi BSc Mashael Alharbi MSc Monira Alaujan MSc Abeer Albaz MSc Muruj Tukruni BSc Atef Nehdi PhD Maha-Hamadien Abdulla PhD Sabine Matou-Nasri PhD |
author_sort |
Zeyad Alehaideb PhD |
title |
Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer Cells |
title_short |
Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer Cells |
title_full |
Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer Cells |
title_fullStr |
Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer Cells |
title_full_unstemmed |
Anti-Proliferative and Pro-Apoptotic Effects of (L’Her.) Methanolic Extract in Human Triple-Negative MDA-MB-231 Breast Cancer Cells |
title_sort |
anti-proliferative and pro-apoptotic effects of (l’her.) methanolic extract in human triple-negative mda-mb-231 breast cancer cells |
publisher |
SAGE Publishing |
series |
Journal of Evidence-Based Integrative Medicine |
issn |
2515-690X |
publishDate |
2020-12-01 |
description |
Triple-negative breast cancer (TNBC), the most aggressive subtype, does not respond to targeted therapy due to the lack of hormone receptors. There is an urgent need for alternative therapies, including natural product-based anti-cancer drugs, at lower cost. We investigated the impact of a Calligonum comosum L’Hér. methanolic extract (CcME) on the TNBC MDA-MB-231 cell line proliferation and related cell death mechanisms performing cell viability and cytotoxicity assays, flow cytometry to detect apoptosis and cell cycle analysis. The apoptosis-related protein array and cellular reactive oxygen species (ROS) assay were also carried out. We showed that the CcME inhibited the TNBC cell viability, in a dose-dependent manner, with low cytotoxic effects. The CcME-treated TNBC cells underwent apoptosis, associated with a concomitant increase of apoptosis-related protein expression, including cytochrome c, cleaved caspase-3, cyclin-dependent kinase inhibitor p21, and the anti-oxidant enzyme catalase, compared with the untreated cells. The CcME also enhanced the mitochondrial transition pore opening activity and induced G 0 /G 1 cell growth arrest, which confirmed the cytochrome c release and the increase of the p21 expression detected in the CcME-treated TNBC cells. The CcME-treated TNBC cells resulted in intracellular ROS production, which, when blocked with a ROS scavenger, did not reduce the CcME-induced apoptosis. In conclusion, CcME exerts anti-proliferative effects against TNBC cells through the induction of apoptosis and cell growth arrest. In vivo studies are justified to verify the CcME anti-proliferative activities and to investigate any potential anti-metastatic activities of CcME against TNBC development and progression. |
url |
https://doi.org/10.1177/2515690X20978391 |
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