Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line
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 Press Ltd
2015
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| Online Access: | http://umpir.ump.edu.my/id/eprint/11270/1/Synthesis%20of%20an%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2-M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20line.pdf |
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| author | Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen |
| author_facet | Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen |
| author_sort | Swee, Keong Yeap |
| collection | UMP |
| 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 | 2024-03-06T11:59:09Z |
| format | Article |
| id | UMPir11270 |
| institution | Universiti Malaysia Pahang |
| language | English |
| last_indexed | 2024-03-06T11:59:09Z |
| publishDate | 2015 |
| publisher | Dove Press Ltd |
| record_format | dspace |
| spelling | UMPir112702018-04-19T02:41:40Z http://umpir.ump.edu.my/id/eprint/11270/ Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen Q Science (General) 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 Press Ltd 2015 Article PeerReviewed application/pdf en cc_by_nc http://umpir.ump.edu.my/id/eprint/11270/1/Synthesis%20of%20an%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2-M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20line.pdf Swee, Keong Yeap and Akhtar, Muhammad Nadeem and Kian, Lam Lim and Nadiah, Abu and Wan, Yong Ho and Seema, Zareen and Kiarash, Roohani and Huynh, Ky and Sheau, Wei Tan and Nordin, Lajis and Noorjahan Banu, Alitheen (2015) Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line. Drug Design, Development and Therapy, 9. pp. 983-992. ISSN 1177-8881. (Published) http://dx.doi.org/10.2147/DDDT.S65468 DOI: 10.2147/DDDT.S65468 |
| spellingShingle | Q Science (General) Swee, Keong Yeap Akhtar, Muhammad Nadeem Kian, Lam Lim Nadiah, Abu Wan, Yong Ho Seema, Zareen Kiarash, Roohani Huynh, Ky Sheau, Wei Tan Nordin, Lajis Noorjahan Banu, Alitheen Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line |
| title | Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line |
| title_full | Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line |
| title_fullStr | Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line |
| title_full_unstemmed | Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line |
| title_short | Synthesis of an Anthraquinone Derivative (DHAQC) and its Effect on Induction of G2/M Arrest and Apoptosis in Breast Cancer MCF-7 Cell Line |
| title_sort | synthesis of an anthraquinone derivative dhaqc and its effect on induction of g2 m arrest and apoptosis in breast cancer mcf 7 cell line |
| topic | Q Science (General) |
| url | http://umpir.ump.edu.my/id/eprint/11270/1/Synthesis%20of%20an%20anthraquinone%20derivative%20%28DHAQC%29%20and%20its%20effect%20on%20induction%20of%20G2-M%20arrest%20and%20apoptosis%20in%20breast%20cancer%20MCF-7%20cell%20line.pdf |
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