Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line

Anthraquinones are an important class of naturally occurring biologically active compounds. In this study, anthraquinone derivative 1,3-dihydroxy-9,10-anthraquinone-2- carboxylic acid (DHAQC) (2) was synthesized with 32% yield through the Friedel–Crafts condensation reaction. The mechanisms of cytot...

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Main Authors:	Swee, Keong Yeap, Akhtar, Muhammad Nadeem, Kian, Lam Lim, Nadiah, Abu, Wan, Yong Ho, Seema, Zareen, Kiarash, Roohani, Huynh, Ky, Sheau, Wei Tan, Nordin, Lajis, Noorjahan Banu, Alitheen
Format:	Article
Language:	English
Published:	Dove Press Ltd 2015
Subjects:	Q Science (General)
Online Access:	http://umpir.ump.edu.my/id/eprint/11270/ http://umpir.ump.edu.my/id/eprint/11270/ http://umpir.ump.edu.my/id/eprint/11270/ http://umpir.ump.edu.my/id/eprint/11270/1/Synthesis%20of%20an%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2-M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20line.pdf

id	ump-11270
recordtype	eprints
spelling	ump-112702018-04-19T02:41:40Z http://umpir.ump.edu.my/id/eprint/11270/ Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen Q Science (General) Anthraquinones are an important class of naturally occurring biologically active compounds. In this study, anthraquinone derivative 1,3-dihydroxy-9,10-anthraquinone-2- carboxylic acid (DHAQC) (2) was synthesized with 32% yield through the Friedel–Crafts condensation reaction. The mechanisms of cytotoxicity of DHAQC (2) in human breast cancer MCF-7 cells were further investigated. Results from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DHAQC (2) exhibited potential cytotoxicity and selectivity in the MCF-7 cell line, comparable with the naturally occurring anthraquinone damnacanthal. DHAQC (2) showed a slightly higher IC50 (inhibitory concentration with 50% cell viability) value in the MCF-7 cell line compared to damnacanthal, but it is more selective in terms of the ratio of IC50 on MCF-7 cells and normal MCF-10A cells. (selective index for DHAQC (2) was 2.3 and 1.7 for damnacanthal). The flow cytometry cell cycle analysis on the MCF-7 cell line treated with the IC50 dose of DHAQC (2) for 48 hours showed that DHAQC (2) arrested MCF-7 cell line at the G2/M phase in association with an inhibited expression of PLK1 genes. Western blot analysis also indicated that the DHAQC (2) increased BAX, p53, and cytochrome c levels in MCF-7 cells, which subsequently activated apoptosis as observed in annexin V/propidium iodide and cell cycle analyses. These results indicate that DHAQC (2) is a synthetic, cytotoxic, and selective anthraquinone, which is less toxic than the natural product damnacanthal, and which demonstrates potential in the induction of apoptosis in the breast cancer MCF-7 cell line. Dove Press Ltd 2015 Article PeerReviewed application/pdf en cc_by_nc http://umpir.ump.edu.my/id/eprint/11270/1/Synthesis%20of%20an%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2-M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20line.pdf Swee, Keong Yeap and Akhtar, Muhammad Nadeem and Kian, Lam Lim and Nadiah, Abu and Wan, Yong Ho and Seema, Zareen and Kiarash, Roohani and Huynh, Ky and Sheau, Wei Tan and Nordin, Lajis and Noorjahan Banu, Alitheen (2015) Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line. Drug Design, Development and Therapy, 9. pp. 983-992. ISSN 1177-8881 http://dx.doi.org/10.2147/DDDT.S65468 DOI: 10.2147/DDDT.S65468
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Malaysia Pahang
building	UMP Institutional Repository
collection	Online Access
language	English
topic	Q Science (General)
spellingShingle	Q Science (General) Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line
description	Anthraquinones are an important class of naturally occurring biologically active compounds. In this study, anthraquinone derivative 1,3-dihydroxy-9,10-anthraquinone-2- carboxylic acid (DHAQC) (2) was synthesized with 32% yield through the Friedel–Crafts condensation reaction. The mechanisms of cytotoxicity of DHAQC (2) in human breast cancer MCF-7 cells were further investigated. Results from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DHAQC (2) exhibited potential cytotoxicity and selectivity in the MCF-7 cell line, comparable with the naturally occurring anthraquinone damnacanthal. DHAQC (2) showed a slightly higher IC50 (inhibitory concentration with 50% cell viability) value in the MCF-7 cell line compared to damnacanthal, but it is more selective in terms of the ratio of IC50 on MCF-7 cells and normal MCF-10A cells. (selective index for DHAQC (2) was 2.3 and 1.7 for damnacanthal). The flow cytometry cell cycle analysis on the MCF-7 cell line treated with the IC50 dose of DHAQC (2) for 48 hours showed that DHAQC (2) arrested MCF-7 cell line at the G2/M phase in association with an inhibited expression of PLK1 genes. Western blot analysis also indicated that the DHAQC (2) increased BAX, p53, and cytochrome c levels in MCF-7 cells, which subsequently activated apoptosis as observed in annexin V/propidium iodide and cell cycle analyses. These results indicate that DHAQC (2) is a synthetic, cytotoxic, and selective anthraquinone, which is less toxic than the natural product damnacanthal, and which demonstrates potential in the induction of apoptosis in the breast cancer MCF-7 cell line.
format	Article
author	Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen
author_facet	Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen
author_sort	Swee, Keong Yeap
title	Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line
title_short	Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line
title_full	Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line
title_fullStr	Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line
title_full_unstemmed	Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line
title_sort	synthesis of an anthraquinone derivative (dhaqc) and its effect on induction of g2/m arrest and apoptosis in breast cancer mcf-7 cell line
publisher	Dove Press Ltd
publishDate	2015
url	http://umpir.ump.edu.my/id/eprint/11270/ http://umpir.ump.edu.my/id/eprint/11270/ http://umpir.ump.edu.my/id/eprint/11270/ http://umpir.ump.edu.my/id/eprint/11270/1/Synthesis%20of%20an%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2-M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20line.pdf
first_indexed	2023-09-18T22:11:50Z
last_indexed	2023-09-18T22:11:50Z
_version_	1777415078813892608

Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line

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