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

Ali, N.M. and Akhtar, M.N. and Ky, H. and Lim, K.L. and Abu, N. and Zareen, S. and Ho, W.Y. and Alan-Ong, H.K. and Tan, S.W. and Alitheen, N.B. and Ismail, J.B. and Yeap, S.K. and Kamarul, T. (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, DOI https://doi.org/10.2147/DDDT.S102164.

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Official URL: https://doi.org/10.2147/DDDT.S102164


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.

Item Type: Article
Funders: University of Malaya HIR-MoE grant (reference number - UM.C/625/1/HIR/ MOHE/CHAN/03, account number - A000003-50001), University Malaysia Pahang internal grants no (RDU 120373 and University Malaysia Pahang internal RDU 120389)
Uncontrolled Keywords: (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS); MCF-7; G2/M arrest; Apoptosis; Cell cycle; PLK-1; p53; Caspase
Subjects: Q Science > Q Science (General)
R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 13 Nov 2017 02:55
Last Modified: 13 Nov 2017 02:55
URI: http://eprints.um.edu.my/id/eprint/18234

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