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

Content Provider	PubMed Central
Author	Yeap, Sweekeong Akhtar, Muhammad Nadeem Lim, Kian Lam Abu, Nadiah Yong, Ho Wan Zareen, Seema Roohani, Kiarash Huynh, Ky Tan, Sheau Wei Nordin, Lajis Banu, Alitheen Noorjahan
Copyright Year	2015
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.
Related Links	http://dx.doi.org/10.2147/DDDT.S65468
Ending Page	992
Page Count	10
Starting Page	983
File Format	PDF
ISSN	11778881
e-ISSN	11778881
Journal	Drug Design, Development and Therapy
Volume Number	9
Language	English
Publisher	Dove Medical Press
Publisher Date	2015-02-17
Access Restriction	Open
Rights Holder	Dove Medical Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmacology Pharmaceutical Science

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