Abstract | PURPOSE: Our previous data have shown that emodin azide methyl anthraquinone derivative (AMAD) triggered mitochondrial- dependent cell apoptosis involving caspase-8-mediated Bid cleavage, and induced proteasomal degradation of HER2/neu by blocking Her2/neu binding to Hsp90. In the present study, we futher investigated the effect of this compound on the cell cycle and related molecular mechanisms in HER2/neu-overexpressing MDA-MB-453 breast cancer cells. METHODS: The cell cycle distribution was tested by flow cytometry. The expression of cell cycle-related proteins was determined by Western blot analysis; DNA agarose gel electrophoresis was used to examine the apoptosis of MDAMB- 453 cells induced by emodin AMAD. RESULTS: After MDA-MB-453 cells were treated with different concentrations of emodin AMAD for 24 hrs, cells were arrested in G0/G1 phase, and the expression of G0/G1 related proteins c/Myc, Cyclin D1, CDK4 and p-Rb changed. DNA fragmentation appeared on the agarose gel in a concentration- dependent manner. CONCLUSION:
Emodin AMAD induced G0/G1 arrest in Her2/ neu-overexpressing MDA-MB-453 cancer cells. This G0/G1 arrest was associated with decreasing protein expression of c-Myc, Cyclin D1, CDK4, and p-Rb.
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Authors | Yan-yan Yan, Li-wu Fu, Wei Zhang, Hong-shan Ma, Cun-gen Ma, Yong-ju Liang, Bin-yu Liu, Jie-zhong Yu, Qiu-zhen Wu, Yi-min Dong |
Journal | Journal of B.U.ON. : official journal of the Balkan Union of Oncology
(J BUON)
2014 Jul-Sep
Vol. 19
Issue 3
Pg. 650-5
ISSN: 1107-0625 [Print] Cyprus |
PMID | 25261647
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 6-azidomethyl-1-hydroxy-3,8-dimethoxy-9,10-anthraquinone
- Anthraquinones
- Antineoplastic Agents
- Azides
- CCND1 protein, human
- Cyclin D1
- ERBB2 protein, human
- Receptor, ErbB-2
- CDK4 protein, human
- Cyclin-Dependent Kinase 4
- Emodin
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Topics |
- Anthraquinones
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Azides
(pharmacology)
- Cell Cycle Checkpoints
(drug effects)
- Cell Line, Tumor
- Cyclin D1
(analysis)
- Cyclin-Dependent Kinase 4
(analysis)
- Emodin
(analogs & derivatives, pharmacology)
- Female
- G1 Phase
(drug effects)
- Humans
- Receptor, ErbB-2
(analysis)
- Resting Phase, Cell Cycle
(drug effects)
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