Synthetic Curcumin Derivative DK1 Possessed G2M Arrest and Induced Apoptosis Through Accumulation of Intracellular ROS in MCF-7 Breast Cancer Cells
Aims: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmaco logical activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BioMed Central
2017
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| Subjects: | |
| Online Access: | http://umpir.ump.edu.my/id/eprint/17149/ http://umpir.ump.edu.my/id/eprint/17149/ http://umpir.ump.edu.my/id/eprint/17149/ http://umpir.ump.edu.my/id/eprint/17149/1/Synthetic%20curcumin%20derivative%20DK1%20possessed%20G2M%20arrest%20and%20induced%20apoptosis%20through%20accumulation%20of%20intracellular%20ROS%20in%20MCF-7%20breast%20cancer%20cells.pdf |
| Summary: | Aims: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmaco logical activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability. Main methods: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels. Key findings: DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9. Significance: DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein. |
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