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学科主题: 药学
题名:
Cell cycle arrest, apoptosis and autophagy induced by iminosugars on K562 cells
作者: Zhu, Jingjing1,2,3; Zhou, Yifa1; Wang, Guan-Nan2,3; Tai, Guihua1; Ye, Xin-Shan2,3
关键词: Iminosugar ; Antitumor ; Apoptosis ; Cell cycle ; Autophagy ; K562 cell line
刊名: EUROPEAN JOURNAL OF PHARMACOLOGY
发表日期: 2014-05-15
DOI: 10.1016/j.ejphar.2014.03.013
卷: 731, 页:65-72
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: POTENTIAL IMMUNOSUPPRESSIVE AGENTS ; CANCER-CELLS ; BIOLOGICAL-ACTIVITY ; BETA-GLUCOSIDASE ; GAUCHER-DISEASE ; MTOR ; INHIBITORS ; DERIVATIVES ; DEATH ; HSP70
英文摘要:

Iminosugars have gained a remarkable importance as new therapeutic agents since 1966. In this study, compounds A and B, two iminosugar analogs synthesized previously, showed an inhibition of the growth of 1(562 cells. They allowed cell cycle arrested at the G(0)/G(1) phase, promoted apoptotic activities and also lowered the mitochondrial membrane potential. Further exploration of the apoptosis mechanism revealed that compound B significantly suppressed the expression of Hsp70, which is a major anti-apoptotic molecular chaperone. Significant decrease was also found in the expression of Akt, a serine/threonine-specific protein kinase with anti-apoptosis activities also known as protein kinase B (PKB). At mitochondria level in comparison with compound A, compound B brought a better promotion in the expression of pro-apoptotic protein Bad in Bcl-2 family. As a result of the promotion, the expression of anti-apoptotic protein Bcl-xL was clown-regulated. Cytochrome c was released, activating the intrinsic signaling pathways of caspase and resulting in the occurrence of cascade reaction. In addition, compound B stimulated autophagy effectively by up-regulating Beclin 1, thus causing the conversion of LC3-I to LC3-II through Akt/mTOR signaling pathway. In summary, these results indicated that compounds A and B induced cell death through multiple pathways. The disclosed results not only provide an evidence of antitumor activity of iminosugars as a foundation for further studies, but also may find potential applications in chronic myeloid leukemia therapy as new heat shock protein inhibitors and autophagy inducer. (C) 2014 Elsevier B.V. All rights reserved.

语种: 英语
WOS记录号: WOS:000334847600009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56052
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.NE Normal Univ, Sch Life Sci, Changchun 130024, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Zhu, Jingjing,Zhou, Yifa,Wang, Guan-Nan,et al. Cell cycle arrest, apoptosis and autophagy induced by iminosugars on K562 cells[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2014,731:65-72.
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