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

Norlaily Mohd Ali, M. Nadeem Akhtar, Huynh Ky, Kian Lam Lim, Nadiah Abu, Seema Zareen, Wan Yong Ho, Han Kiat Alan-Ong, Sheau Wei Tan, Noorjahan Banu Alitheen, Jamil Bin Ismail, Swee Keong Yeap, Tunku Kamarul

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1897-1907
Number of pages11
JournalDrug Design, Development and Therapy
Volume10
DOIs
Publication statusPublished - 10 Jun 2016
Externally publishedYes

Fingerprint

MCF-7 Cells
Chalcones
Apoptosis
Breast Neoplasms
Inhibitory Concentration 50
Cell Line
Spectrum Analysis
Electrons
Caspase 9
DNA Fragmentation
Centers for Disease Control and Prevention (U.S.)
Real-Time Polymerase Chain Reaction
Flow Cytometry
Breast
Magnetic Resonance Spectroscopy
Western Blotting
Phosphorylation
Light
Pharmaceutical Preparations
Neoplasms

Keywords

  • (E)-1-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS)
  • Apoptosis
  • Caspase
  • Cell cycle
  • G2/M arrest
  • MCF-7
  • P53
  • PLK-1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line. / Ali, Norlaily Mohd; Akhtar, M. Nadeem; Ky, Huynh; Lim, Kian Lam; Abu, Nadiah; Zareen, Seema; Ho, Wan Yong; Alan-Ong, Han Kiat; Tan, Sheau Wei; Alitheen, Noorjahan Banu; Ismail, Jamil Bin; Yeap, Swee Keong; Kamarul, Tunku.

In: Drug Design, Development and Therapy, Vol. 10, 10.06.2016, p. 1897-1907.

Research output: Contribution to journalArticle

Ali, NM, Akhtar, MN, Ky, H, Lim, KL, Abu, N, Zareen, S, Ho, WY, Alan-Ong, HK, Tan, SW, Alitheen, NB, Ismail, JB, Yeap, SK & Kamarul, T 2016, 'Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line', Drug Design, Development and Therapy, vol. 10, pp. 1897-1907. https://doi.org/10.2147/DDDT.S102164
Ali, Norlaily Mohd ; Akhtar, M. Nadeem ; Ky, Huynh ; Lim, Kian Lam ; Abu, Nadiah ; Zareen, Seema ; Ho, Wan Yong ; Alan-Ong, Han Kiat ; Tan, Sheau Wei ; Alitheen, Noorjahan Banu ; Ismail, Jamil Bin ; Yeap, Swee Keong ; Kamarul, Tunku. / Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line. In: Drug Design, Development and Therapy. 2016 ; Vol. 10. pp. 1897-1907.
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AU - Zareen, Seema

AU - Ho, Wan Yong

AU - Alan-Ong, Han Kiat

AU - Tan, Sheau Wei

AU - Alitheen, Noorjahan Banu

AU - Ismail, Jamil Bin

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