Synthesis of an anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell line

Sweekeong Yeap, Muhammad Nadeem Akhtar, Kian Lam Lim, Nadiah Abu, Wan Yong Ho, Seema Zareen, Kiarash Roohani, Huynh Ky, Sheau Wei Tan, Nordin Lajis, Noorjahan Banu Alitheen

Research output: Contribution to journalArticle

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Abstract

Anthraquinones are an important class of naturally occurring biologically active compounds. In this study, anthraquinone derivative 1,3-dihydroxy-9,10-anthraquinone-2-carboxylic acid (DHAQC) (2) was synthesized with 32% yield through the Friedel–Crafts condensation reaction. The mechanisms of cytotoxicity of DHAQC (2) in human breast cancer MCF-7 cells were further investigated. Results from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that DHAQC (2) exhibited potential cytotoxicity and selectivity in the MCF-7 cell line, comparable with the naturally occurring anthraquinone damnacanthal. DHAQC (2) showed a slightly higher IC50 (inhibitory concentration with 50% cell viability) value in the MCF-7 cell line compared to damnacanthal, but it is more selective in terms of the ratio of IC50 on MCF-7 cells and normal MCF-10A cells. (selective index for DHAQC (2) was 2.3 and 1.7 for damnacanthal). The flow cytometry cell cycle analysis on the MCF-7 cell line treated with the IC50 dose of DHAQC (2) for 48 hours showed that DHAQC (2) arrested MCF-7 cell line at the G2/M phase in association with an inhibited expression of PLK1 genes. Western blot analysis also indicated that the DHAQC (2) increased BAX, p53, and cytochrome c levels in MCF-7 cells, which subsequently activated apoptosis as observed in annexin V/propidium iodide and cell cycle analyses. These results indicate that DHAQC (2) is a synthetic, cytotoxic, and selective anthraquinone, which is less toxic than the natural product damnacanthal, and which demonstrates potential in the induction of apoptosis in the breast cancer MCF-7 cell line.

Original languageEnglish
Pages (from-to)983-992
Number of pages10
JournalDrug Design, Development and Therapy
Volume9
DOIs
Publication statusPublished - 17 Feb 2015
Externally publishedYes

Fingerprint

Anthraquinones
MCF-7 Cells
Apoptosis
Breast Neoplasms
Cell Line
Inhibitory Concentration 50
Cell Cycle
1,3-dihydroxy-9,10-anthraquinone-2-carboxylic acid
Propidium
G2 Phase
Poisons
Annexin A5
Cytochromes c
Biological Products
Cell Division
Cell Survival
Flow Cytometry
Western Blotting
Gene Expression
damnacanthal

Keywords

  • Cell cycle
  • Cytotoxic
  • Selective index

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Synthesis of an anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell line. / Yeap, Sweekeong; Akhtar, Muhammad Nadeem; Lim, Kian Lam; Abu, Nadiah; Ho, Wan Yong; Zareen, Seema; Roohani, Kiarash; Ky, Huynh; Tan, Sheau Wei; Lajis, Nordin; Alitheen, Noorjahan Banu.

In: Drug Design, Development and Therapy, Vol. 9, 17.02.2015, p. 983-992.

Research output: Contribution to journalArticle

Yeap, Sweekeong ; Akhtar, Muhammad Nadeem ; Lim, Kian Lam ; Abu, Nadiah ; Ho, Wan Yong ; Zareen, Seema ; Roohani, Kiarash ; Ky, Huynh ; Tan, Sheau Wei ; Lajis, Nordin ; Alitheen, Noorjahan Banu. / Synthesis of an anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell line. In: Drug Design, Development and Therapy. 2015 ; Vol. 9. pp. 983-992.
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