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

Authors Yeap S, Akhtar MN, Lim KL, Abu N, Ho WY, Zareen S, Roohani K, Ky H, Tan SW, Lajis N, Mohamed Alitheen NB

Received 3 April 2014

Accepted for publication 7 May 2014

Published 17 February 2015 Volume 2015:9 Pages 983—992

DOI https://doi.org/10.2147/DDDT.S65468

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4


SweeKeong Yeap,1 Muhammad Nadeem Akhtar,2 Kian Lam Lim,3 Nadiah Abu,4,5 Wan Yong Ho,6 Seema Zareen,2 Kiarash Roohani,1 Huynh Ky,4 Sheau Wei Tan,1 Nordin Lajis,7 Noorjahan Banu Alitheen1,4

1Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 2Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Kuantan, Pahang, Malaysia; 3Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor Darul Ehsan, Malaysia; 4Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 5Bright Sparks Unit, University of Malaya, Kuala Lumpur, Malaysia; 6School of Biomedical Sciences, University of Nottingham Malaysia Campus, Selangor Darul Ehsan, Malaysia; 7Scientific Chairs Unit, Taibah University, Medina, Saudi Arabia

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.

Keywords: cytotoxic, selective index, cell cycle


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