Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines
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 cytot...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/46467/ http://psasir.upm.edu.my/id/eprint/46467/1/Synthesis%20of%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20lines.pdf |
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| author | Yeap, Swee Keong Akhtar, Muhammad Nadeem Kian, Lam Lim Abu, Nadiah Wan, Yong Ho Zareen, Seema Roohani, Kiarash Huynh, Ky Sheau, Wei Tan Lajis, Md. Nordin Mohamed Alitheen, Noorjahan Banu |
| author_facet | Yeap, Swee Keong Akhtar, Muhammad Nadeem Kian, Lam Lim Abu, Nadiah Wan, Yong Ho Zareen, Seema Roohani, Kiarash Huynh, Ky Sheau, Wei Tan Lajis, Md. Nordin Mohamed Alitheen, Noorjahan Banu |
| author_sort | Yeap, Swee Keong |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T10:09:54Z |
| format | Article |
| id | upm-46467 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T10:09:54Z |
| publishDate | 2015 |
| publisher | Dove Medical Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-464672018-03-27T01:19:39Z http://psasir.upm.edu.my/id/eprint/46467/ Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines Yeap, Swee Keong Akhtar, Muhammad Nadeem Kian, Lam Lim Abu, Nadiah Wan, Yong Ho Zareen, Seema Roohani, Kiarash Huynh, Ky Sheau, Wei Tan Lajis, Md. Nordin Mohamed Alitheen, Noorjahan Banu 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. Dove Medical Press 2015 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/46467/1/Synthesis%20of%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20lines.pdf Yeap, Swee Keong and Akhtar, Muhammad Nadeem and Kian, Lam Lim and Abu, Nadiah and Wan, Yong Ho and Zareen, Seema and Roohani, Kiarash and Huynh, Ky and Sheau, Wei Tan and Lajis, Md. Nordin and Mohamed Alitheen, Noorjahan Banu (2015) Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines. Drug Design, Development and Therapy, 9. pp. 983-992. ISSN ESSN: 1177-8881 http://www.dovepress.com/drug-design-development-and-therapy-journal 10.2147/DDDT.S65468 |
| spellingShingle | Yeap, Swee Keong Akhtar, Muhammad Nadeem Kian, Lam Lim Abu, Nadiah Wan, Yong Ho Zareen, Seema Roohani, Kiarash Huynh, Ky Sheau, Wei Tan Lajis, Md. Nordin Mohamed Alitheen, Noorjahan Banu Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines |
| title | Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines |
| title_full | Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines |
| title_fullStr | Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines |
| title_full_unstemmed | Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines |
| title_short | Synthesis of anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell lines |
| title_sort | synthesis of anthraquinone derivative (dhaqc) and its effect on induction of g2/m arrest and apoptosis in breast cancer mcf-7 cell lines |
| url | http://psasir.upm.edu.my/id/eprint/46467/ http://psasir.upm.edu.my/id/eprint/46467/ http://psasir.upm.edu.my/id/eprint/46467/ http://psasir.upm.edu.my/id/eprint/46467/1/Synthesis%20of%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20lines.pdf |