Catechins induced acute promyelocytic leukemia cell apoptosis and triggered PML-RARα oncoprotein degradation
| Autor: | Qiu-sheng Chen, Xiang-qin Wen, Dan Xiao, Ying Qian, Wei-Li Zhao, Yan Zhao, Li Zhang, Yan Sheng, Ai-Hua Wang, Pengpeng Xu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Acute promyelocytic leukemia Cancer Research Oncogene Proteins Fusion Cell Survival Blotting Western Mice Nude Apoptosis Biology Catechin Catechins Flow cytometry Mice Leukemia Promyelocytic Acute Western blot Cell Line Tumor In Situ Nick-End Labeling medicine Animals Humans MTT assay Viability assay Molecular Biology Tea medicine.diagnostic_test Cell growth Research Hematology Flow Cytometry medicine.disease Xenograft Model Antitumor Assays Molecular biology Oncology PML-RARα oncoprotein Cell culture |
| Zdroj: | Journal of Hematology & Oncology |
| ISSN: | 1756-8722 |
| DOI: | 10.1186/s13045-014-0075-3 |
| Popis: | Background It has recently been reported that the extracts of green tea polyphenol have cancer preventive effects. In this study, we investigated the effect of the natural composition from green tea leaves Catechins on acute promyelocytic leukemia (APL). Methods In vitro, APL cell lines NB4, retinoic acid-resistant NB4-R1 and NB4-R2 were treated with different concentrations of Catechins. Cell viability and cell apoptosis were analyzed using MTT assay and flow cytometric assay, respectively. Expression of proteins related to apoptosis and PML-RARα oncoprotein were assessed by Western blot. In vivo anti-tumor activity of Catechins was examined in nude mice xenografted with NB4 cells and in situ cell apoptosis was detected by terminal deoxytransferase-catalyzed DNA nick-end labeling assay. Results Catechins at micromolar concentration levels significantly inhibited APL cell proliferation and induced cell apoptosis, in association with mitochondria damage, ROS production and caspase activation. The anti-apoptotic Bcl-2 family member Bcl-xL was down regulated, with pro-apoptotic member Bax remaining unchanged. Moreover, Catechins induced the degradation of PML-RARα oncoprotein. Catechins-mediated apoptotic effect was also observed in primary APL cells without affecting normal hematopoietic progenitor cells. In the murine xenograft model, Catechins remarkably inhibited tumor growth and induced in situ leukemic cell apoptosis. Conclusions Catechins might be a potential candidate for APL treatment by activating intrinsic apoptotic pathway and targeting PML-RARα oncoprotein. |
| Databáze: | OpenAIRE |
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