Spiroquinazolinone-induced cytotoxicity and apoptosis in K562 human leukemia cells: alteration in expression levels of Bcl-2 and Bax
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- Ghasemian Majid
- Department of Biology, Faculty of Natural Science, University of Tabriz, Iran
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- Mahdavi Majid
- Department of Biology, Faculty of Natural Science, University of Tabriz, Iran
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- Zare Payman
- Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Iran
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- Ali Hosseinpour Feizi Mohammad
- Department of Biology, Faculty of Natural Science, University of Tabriz, Iran
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抄録
Spiroquinazolinone compounds have been considered as a new series of potent apoptosis-inducing agents. In this study, anti-proliferative and apoptotic effects of the derivatives from the spiroquinazolinone family were investigated in the human chronic myeloid leukemia K562 cells. The K562 cells were treated with various concentrations of the spiroquinazolinone (10-300 µM) for 3 days and cell viability was determined by MTT growth inhibition assay. 4t-QTC was more active among these compounds with IC50 of 50 ± 3.6 µM and was selected for further studies. Apoptosis, as the mechanism of cell death was investigated morphologically by acridine orange/ethidium bromide (AO/EtBr) double staining, cell surface expression assay of phosphatidyl serine by Annexin V/PI technique, as well as the formation of DNA ladder. The K562 cells underwent apoptosis upon a single dose (at IC50 value) of the 4t-QTC compound, and over-expressed caspase-3 expression by more than 1.7-fold, following a 72 hr treatment. Furthermore, RT-PCR and Western blot analysis revealed that treatment of the K562 cells with 4t-QTC down-regulates and up-regulates the expression of Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic), respectively. Based on the present data, it seems that these compounds from the spiroquinazolinone family are good candidates for further evaluation as an effective chemotherapeutic family acting through induction of apoptosis in chronic myeloid leukemia.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 40 (1), 115-126, 2015
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204905741824
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- NII論文ID
- 130004904026
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- NII書誌ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 026085640
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- PubMed
- 25743751
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可