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:	Ali, N.M., Akhtar, M.N., Ky, H., Lim, K.L., Abu, N., Zareen, S., Ho, W.Y., Alan-Ong, H.K., Tan, S.W., Alitheen, N.B., Ismail, J.B., Yeap, S.K., Kamarul, T.
Format:	Article
Published:	Dove Medical Press 2016
Subjects:	Q Science (General) R Medicine
Online Access:	https://doi.org/10.2147/DDDT.S102164 https://doi.org/10.2147/DDDT.S102164

id	um-18234
recordtype	eprints
spelling	um-182342017-11-13T02:55:15Z Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line Ali, N.M. Akhtar, M.N. Ky, H. Lim, K.L. Abu, N. Zareen, S. Ho, W.Y. Alan-Ong, H.K. Tan, S.W. Alitheen, N.B. Ismail, J.B. Yeap, S.K. Kamarul, T. Q Science (General) R Medicine 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 https://doi.org/10.2147/DDDT.S102164 Ali, N.M.; Akhtar, M.N.; Ky, H.; Lim, K.L.; Abu, N.; Zareen, S.; Ho, W.Y.; Alan-Ong, H.K.; Tan, S.W.; Alitheen, N.B.; Ismail, J.B.; Yeap, S.K.; Kamarul, T. (2016) Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line. Drug Design, Development and Therapy <http://eprints.um.edu.my/view/publication/Drug_Design,_Development_and_Therapy.html>, 10. pp. 1897-1907. ISSN 1177-8881 http://eprints.um.edu.my/18234/
repository_type	Digital Repository
institution_category	Local University
institution	University Malaya
building	UM Research Repository
collection	Online Access
topic	Q Science (General) R Medicine
spellingShingle	Q Science (General) R Medicine Ali, N.M. Akhtar, M.N. Ky, H. Lim, K.L. Abu, N. Zareen, S. Ho, W.Y. Alan-Ong, H.K. Tan, S.W. Alitheen, N.B. Ismail, J.B. Yeap, S.K. Kamarul, T. 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	Ali, N.M. Akhtar, M.N. Ky, H. Lim, K.L. Abu, N. Zareen, S. Ho, W.Y. Alan-Ong, H.K. Tan, S.W. Alitheen, N.B. Ismail, J.B. Yeap, S.K. Kamarul, T.
author_facet	Ali, N.M. Akhtar, M.N. Ky, H. Lim, K.L. Abu, N. Zareen, S. Ho, W.Y. Alan-Ong, H.K. Tan, S.W. Alitheen, N.B. Ismail, J.B. Yeap, S.K. Kamarul, T.
author_sort	Ali, N.M.
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	https://doi.org/10.2147/DDDT.S102164 https://doi.org/10.2147/DDDT.S102164
first_indexed	2018-09-06T06:49:08Z
last_indexed	2018-09-06T06:49:08Z
_version_	1610839803261091840

Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line

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