A polymethoxyflavone from Laggera pterodonta induces apoptosis in imatinib-resistant K562R cells via activation of the intrinsic apoptosis pathway
| Autor: | Bailian Liu, Yangqiu Li, Yuhong Lu, Bo Li, Changshu Cao, Chengwu Zeng, Yaolan Li, Shaohua Chen, Lijian Yang |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Cancer Research
ABL medicine.diagnostic_test business.industry medicine.drug_class Cell growth Intrinsic apoptosis Apoptosis Imatinib-resistant K562 cells DHTMF Tyrosine-kinase inhibitor Flow cytometry Imatinib mesylate Oncology Immunology Cancer research Genetics Medicine Primary Research business Tyrosine kinase Cell proliferation |
| Zdroj: | Cancer Cell International |
| ISSN: | 1475-2867 |
| DOI: | 10.1186/s12935-014-0137-1 |
| Popis: | Background Treatment with imatinib mesylate (IM) (a tyrosine kinase inhibitor) is the first line of standard care for patients newly diagnosed with CML. Despite the success of IM and other tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) remains largely incurable, and a number of CML patients die due to Abl mutation-related drug resistance and blast crisis. 3, 5-Dihydroxy-6, 7, 3′4′-tetramethoxyflavone (DHTMF) is a polymethoxyflavone isolated from Laggera pterodonta which is a herbal medicine used to treat cancer in the Chinese folk. In the previous study, we found DHTMF demonstrated good antiproliferative activities against a number of cancer cell lines and induced the apoptosis of CNE cells in vitro in a time- and dose-dependent manner while exhibiting low cytotoxicity in the two normal cell lines Vero and EVC304. The aim of the present study was to evaluate the proliferation inhibition and apoptosis induced by DHTMF alone and in combination with IM in the IM-resistant CML cell line K562R. Methods Cell proliferation was assayed with the cell counting kit-8 (CCK8) method. The apoptosis percentage was determined by flow cytometry (FCM). Mitochondrial transmembrane potential was detected using FCM and confocal laser-scanning microscopy. The level of proteins involved in apoptosis was detected by Western blotting. Results DHTMF suppressed K562R cell viability in both time- and dose-dependent manners. DHTMF combined with IM enhanced the inhibitory effects and apoptosis in K562R cells as compared with DHTMF alone. DHTMF alone and in combination with IM significantly decreased the mitochondrial membrane potential and increased the levels of cleaved caspase-9, caspase-7, caspase-3, and PARP in K562R cells. Conclusions We demonstrated that DHTMF could inhibit IM-resistant K562R cell proliferation and induces apoptosis via the intrinsic mitochondrial apoptotic pathway. These results suggest that DHTMF may be a potential therapeutic drug with lower side effects against IM resistance in CML cells. |
| Databáze: | OpenAIRE |
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