Affiliations 

  • 1 Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia
  • 2 Department of Industrial Biotechnology, Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Pahang, Malaysia
  • 3 Department of Agriculture Genetics and Breeding, College of Agriculture and Applied Biology, Cantho University, CanTho City, Vietnam
  • 4 Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor, Malaysia
  • 5 School of Biomedical Sciences, The University of Nottingham Malaysia Campus, Selangor, Malaysia
  • 6 Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia
  • 7 Tissue Engineering Group, National Orthopaedic Centre of Excellence for Research and Learning, Department of Orthopaedic Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
Drug Des Devel Ther, 2016;10:1897-907.
PMID: 27358555 DOI: 10.2147/DDDT.S102164

Abstract

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 (1)H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet ((1)H 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.