Staff View: Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells

Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells

Aims: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended a...

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Main Authors:	Mohd Ali, Norlaily, Swee, Keong Yeap, Abu, Nadiah, Kian, Lam Lim, Ky, Huynh, Pauzi, Ahmad Zaim Mat, Wan, Yong Ho, Sheau, Wei Tan, Alan‑Ong, Han Kiat, Zareen, Seema, Alitheen, Noorjahan Banu, Akhtar, M. Nadeem
Format:	Article
Language:	English
Published:	BioMed Central 2017
Online Access:	http://psasir.upm.edu.my/id/eprint/63373/1/Synthetic%20curcumin%20derivative%20DK1%20possessed%20G2M%20arrest%20and%20induced%20apoptosis%20through%20accumulation%20of%20intracellular%20ROS%20in%20MCF-7%20breast%20cancer%20cells.pdf http://psasir.upm.edu.my/id/eprint/63373/
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spelling	my.upm.eprints.633732018-10-16T09:27:30Z http://psasir.upm.edu.my/id/eprint/63373/ Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells Mohd Ali, Norlaily Swee, Keong Yeap Abu, Nadiah Kian, Lam Lim Ky, Huynh Pauzi, Ahmad Zaim Mat Wan, Yong Ho Sheau, Wei Tan Alan‑Ong, Han Kiat Zareen, Seema Alitheen, Noorjahan Banu Akhtar, M. Nadeem Aims: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability. Main methods: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels. Key findings: DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9. Significance: DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein. BioMed Central 2017-08 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/63373/1/Synthetic%20curcumin%20derivative%20DK1%20possessed%20G2M%20arrest%20and%20induced%20apoptosis%20through%20accumulation%20of%20intracellular%20ROS%20in%20MCF-7%20breast%20cancer%20cells.pdf Mohd Ali, Norlaily and Swee, Keong Yeap and Abu, Nadiah and Kian, Lam Lim and Ky, Huynh and Pauzi, Ahmad Zaim Mat and Wan, Yong Ho and Sheau, Wei Tan and Alan‑Ong, Han Kiat and Zareen, Seema and Alitheen, Noorjahan Banu and Akhtar, M. Nadeem (2017) Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells. Cancer Cell International, 17 (30). pp. 1-12. ISSN 1475-2867; ESSN: 1475-2867 10.1186/s12935-017-0400-3
institution	Universiti Putra Malaysia
building	UPM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Putra Malaysia
content_source	UPM Institutional Repository
url_provider	http://psasir.upm.edu.my/
language	English
description	Aims: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability. Main methods: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels. Key findings: DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9. Significance: DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein.
format	Article
author	Mohd Ali, Norlaily Swee, Keong Yeap Abu, Nadiah Kian, Lam Lim Ky, Huynh Pauzi, Ahmad Zaim Mat Wan, Yong Ho Sheau, Wei Tan Alan‑Ong, Han Kiat Zareen, Seema Alitheen, Noorjahan Banu Akhtar, M. Nadeem
spellingShingle	Mohd Ali, Norlaily Swee, Keong Yeap Abu, Nadiah Kian, Lam Lim Ky, Huynh Pauzi, Ahmad Zaim Mat Wan, Yong Ho Sheau, Wei Tan Alan‑Ong, Han Kiat Zareen, Seema Alitheen, Noorjahan Banu Akhtar, M. Nadeem Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells
author_facet	Mohd Ali, Norlaily Swee, Keong Yeap Abu, Nadiah Kian, Lam Lim Ky, Huynh Pauzi, Ahmad Zaim Mat Wan, Yong Ho Sheau, Wei Tan Alan‑Ong, Han Kiat Zareen, Seema Alitheen, Noorjahan Banu Akhtar, M. Nadeem
author_sort	Mohd Ali, Norlaily
title	Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells
title_short	Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells
title_full	Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells
title_fullStr	Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells
title_full_unstemmed	Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells
title_sort	synthetic curcumin derivative dk1 possessed g2/m arrest and induced apoptosis through accumulation of intracellular ros in mcf-7 breast cancer cells
publisher	BioMed Central
publishDate	2017
url	http://psasir.upm.edu.my/id/eprint/63373/1/Synthetic%20curcumin%20derivative%20DK1%20possessed%20G2M%20arrest%20and%20induced%20apoptosis%20through%20accumulation%20of%20intracellular%20ROS%20in%20MCF-7%20breast%20cancer%20cells.pdf http://psasir.upm.edu.my/id/eprint/63373/
_version_	1643837784857772032
score	13.211869

Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells

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