Staff View: Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells

Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells

The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazoli...

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Main Authors:	Zahedifard, M., Faraj, F.L., Paydar, M., Looi, C.Y., Hasandarvish, P., Hajrezaie, M., Kamalidehghan, B., Majid, N.A., Khalifa, S.A.M., Ali, H.M., Abdulla, M.A., El-Seedi, H.R.
Format:	Article
Published:	Bentham Science Publishers 2015
Subjects:	Q Science (General) R Medicine
Online Access:	http://eprints.um.edu.my/19314/ http://dx.doi.org/10.2174/1381612821666150326104952
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spelling	my.um.eprints.193142018-09-20T03:36:23Z http://eprints.um.edu.my/19314/ Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells Zahedifard, M. Faraj, F.L. Paydar, M. Looi, C.Y. Hasandarvish, P. Hajrezaie, M. Kamalidehghan, B. Majid, N.A. Khalifa, S.A.M. Ali, H.M. Abdulla, M.A. El-Seedi, H.R. Q Science (General) R Medicine The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2-hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis. Bentham Science Publishers 2015 Article PeerReviewed Zahedifard, M. and Faraj, F.L. and Paydar, M. and Looi, C.Y. and Hasandarvish, P. and Hajrezaie, M. and Kamalidehghan, B. and Majid, N.A. and Khalifa, S.A.M. and Ali, H.M. and Abdulla, M.A. and El-Seedi, H.R. (2015) Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells. Current Pharmaceutical Design, 21 (23). pp. 3417-3426. ISSN 1381-6128 http://dx.doi.org/10.2174/1381612821666150326104952 doi:10.2174/1381612821666150326104952
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	Q Science (General) R Medicine
spellingShingle	Q Science (General) R Medicine Zahedifard, M. Faraj, F.L. Paydar, M. Looi, C.Y. Hasandarvish, P. Hajrezaie, M. Kamalidehghan, B. Majid, N.A. Khalifa, S.A.M. Ali, H.M. Abdulla, M.A. El-Seedi, H.R. Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
description	The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2-hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.
format	Article
author	Zahedifard, M. Faraj, F.L. Paydar, M. Looi, C.Y. Hasandarvish, P. Hajrezaie, M. Kamalidehghan, B. Majid, N.A. Khalifa, S.A.M. Ali, H.M. Abdulla, M.A. El-Seedi, H.R.
author_facet	Zahedifard, M. Faraj, F.L. Paydar, M. Looi, C.Y. Hasandarvish, P. Hajrezaie, M. Kamalidehghan, B. Majid, N.A. Khalifa, S.A.M. Ali, H.M. Abdulla, M.A. El-Seedi, H.R.
author_sort	Zahedifard, M.
title	Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
title_short	Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
title_full	Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
title_fullStr	Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
title_full_unstemmed	Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells
title_sort	synthesis of apoptotic new quinazolinone-based compound and identification of its underlying mitochondrial signalling pathway in breast cancer cells
publisher	Bentham Science Publishers
publishDate	2015
url	http://eprints.um.edu.my/19314/ http://dx.doi.org/10.2174/1381612821666150326104952
_version_	1643690951354351616
score	13.211869

Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells

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