Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line
Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with 1H-nuclear magne...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2016
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| Online Access: | http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/1/fist-2016-nadeem-Flavokawain%20derivative%20FLS2.pdf |
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| author | Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul |
| author_facet | Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul |
| author_sort | Norlaily, Mohd Ali |
| building | UMP Institutional Repository |
| collection | Online Access |
| description | Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with 1H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet (1H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug. |
| first_indexed | 2025-11-15T02:06:56Z |
| format | Article |
| id | ump-16810 |
| institution | Universiti Malaysia Pahang |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T02:06:56Z |
| publishDate | 2016 |
| publisher | Dove Medical Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | ump-168102017-12-26T03:19:10Z http://umpir.ump.edu.my/id/eprint/16810/ Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul QR Microbiology Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2′-Hydroxy-4′,6′-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with 1H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet (1H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug. Dove Medical Press 2016 Article PeerReviewed application/pdf en http://umpir.ump.edu.my/id/eprint/16810/1/fist-2016-nadeem-Flavokawain%20derivative%20FLS2.pdf Norlaily, Mohd Ali and Akhtar, Muhammad Nadeem and Huynh, Ky and Kian, Lam Lim and Nadiah, Abu and Seema, Zareen and Wan, Yong Ho and Han, Kiat Alan-Ong and Sheau, Wei Tan and Noorjahan Banu, Alitheen and Jamil, Ismail and Swee, Keong Yeap and Tunku, Kamarul (2016) Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line. Drug Design, Development and Therapy, 10. pp. 1897-1907. ISSN 1177-8881. (Published) http://dx.doi.org/10.2147/DDDT.S102164 doi: 10.2147/DDDT.S102164 |
| spellingShingle | QR Microbiology Norlaily, Mohd Ali Akhtar, Muhammad Nadeem Huynh, Ky Kian, Lam Lim Nadiah, Abu Seema, Zareen Wan, Yong Ho Han, Kiat Alan-Ong Sheau, Wei Tan Noorjahan Banu, Alitheen Jamil, Ismail Swee, Keong Yeap Tunku, Kamarul Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line |
| title | Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line |
| title_full | Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line |
| title_fullStr | Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line |
| title_full_unstemmed | Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line |
| title_short | Flavokawain Derivative FLS Induced G2/M Arrest and Apoptosis on Breast Cancer MCF-7 Cell Line |
| title_sort | flavokawain derivative fls induced g2/m arrest and apoptosis on breast cancer mcf-7 cell line |
| topic | QR Microbiology |
| url | http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/ http://umpir.ump.edu.my/id/eprint/16810/1/fist-2016-nadeem-Flavokawain%20derivative%20FLS2.pdf |