Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line

Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with 1H-nuclear magne...

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Main Authors:	Norlaily, Mohd Ali, Akhtar, Muhammad Nadeem, Huynh, Ky, Kian, Lam Lim, Nadiah, Abu, Seema, Zareen, Wan, Yong Ho, Han, Kiat Alan-Ong, Sheau, Wei Tan, Noorjahan Banu, Alitheen, Jamil, Ismail, Swee, Keong Yeap, Tunku, Kamarul
Format:	Article
Language:	English
Published:	Dove Medical Press 2016
Subjects:	QR Microbiology
Online Access:	http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/1/fist-2016-nadeem-Flavokawain%20derivative%20FLS2.pdf

id	ump-16810
recordtype	eprints
spelling	ump-168102017-12-26T03:19:10Z http://umpir.ump.edu.my/id/eprint/16810/ Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul QR Microbiology Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with 1H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet (1H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug. Dove Medical Press 2016 Article PeerReviewed application/pdf en http://umpir.ump.edu.my/id/eprint/16810/1/fist-2016-nadeem-Flavokawain%20derivative%20FLS2.pdf Norlaily, Mohd Ali and Akhtar, Muhammad Nadeem and Huynh, Ky and Kian, Lam Lim and Nadiah, Abu and Seema, Zareen and Wan, Yong Ho and Han, Kiat Alan-Ong and Sheau, Wei Tan and Noorjahan Banu, Alitheen and Jamil, Ismail and Swee, Keong Yeap and Tunku, Kamarul (2016) Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line. Drug Design, Development and Therapy, 10. pp. 1897-1907. ISSN 1177-8881 http://dx.doi.org/10.2147/DDDT.S102164 doi: 10.2147/DDDT.S102164
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Malaysia Pahang
building	UMP Institutional Repository
collection	Online Access
language	English
topic	QR Microbiology
spellingShingle	QR Microbiology Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line
description	Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with 1H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet (1H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug.
format	Article
author	Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul
author_facet	Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul
author_sort	Norlaily, Mohd Ali
title	Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line
title_short	Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line
title_full	Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line
title_fullStr	Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line
title_full_unstemmed	Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line
title_sort	flavokawain derivative fls induced g2/m arrest and apoptosis on breast cancer mcf-7 cell line
publisher	Dove Medical Press
publishDate	2016
url	http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/1/fist-2016-nadeem-Flavokawain%20derivative%20FLS2.pdf
first_indexed	2023-09-18T22:22:49Z
last_indexed	2023-09-18T22:22:49Z
_version_	1777415769760464896

Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line

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