Molecular and Cellular Biochemistry

, Volume 368, Issue 1–2, pp 17–25 | Cite as

Cryptotanshinone induces cell cycle arrest and apoptosis of multidrug resistant human chronic myeloid leukemia cells by inhibiting the activity of eukaryotic initiation factor 4E

  • Yuqing Ge
  • Rubin Cheng
  • Yuhong Zhou
  • Jianping Shen
  • Laijun Peng
  • Xiaofeng Xu
  • Qun Dai
  • Pei Liu
  • Haibing Wang
  • Xiaoqiong Ma
  • Jia Jia
  • Zhe Chen
Article

Abstract

Cryptotanshinone (CPT), a diterpene quinone isolated from Salvia miltiorrhiza, is recently reported to have obvious anticancer activities against diverse cancer cells. However, the effect and regulatory mechanism of CPT remain unclear in human chronic myeloid leukemia (CML) cells. In this study, we investigated the antiproliferative activity of CPT on the multidrug resistant CML cells K562/ADM. Our results demonstrated that CPT decreased the cell viability of K562/ADM cells by inducing cell cycle arrest and apoptosis through suppressing the expression of cyclin D1 and Bcl-2. Further studies indicated that CPT mainly functions at post-transcriptional levels, suggesting the involvement of eukaryotic initiation factor 4E (eIF4E). CPT significantly reduced the expression and activity of eIF4E in K562/ADM cells. Overexpression of eIF4E obvious conferred resistance to the CPT antiproliferation and proapoptotic activity as well as the cyclin D1 and Bcl-2 expressions. Knockdown of eIF4E significantly reduced the inhibitory effect of CPT in K562/ADM, confirming the participation of eIF4E during CPT function process. More importantly, the relative inhibitory efficiency of CPT positively correlated with the reductions on eIF4E in primary CML specimens. These results demonstrated that CPT played antitumor roles in K562/ADM cells by inhibiting the eIF4E regulatory system. Our results provide a novel anticancer mechanism of CPT in human CML cells.

Keywords

Cryptotanshinone Chronic myeloid leukemia Cell cycle arrest Apoptosis eIF4E 

Notes

Acknowledgments

This work was supported by the Special Foundation for Young Scientists of Zhejiang Chinese Medical University (No. 2011ZR05), National Natural Science Foundation of China (No. 30600280), Research Foundation for Traditional Chinese Medicine of Zhejiang Province (No. 2006Y2003) and the Zhejiang Extremely Key Subject of Chinese and Western Integrative Medicine.

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Yuqing Ge
    • 1
  • Rubin Cheng
    • 2
  • Yuhong Zhou
    • 1
  • Jianping Shen
    • 1
  • Laijun Peng
    • 1
  • Xiaofeng Xu
    • 3
  • Qun Dai
    • 1
  • Pei Liu
    • 1
  • Haibing Wang
    • 1
  • Xiaoqiong Ma
    • 1
  • Jia Jia
    • 4
  • Zhe Chen
    • 1
  1. 1.Zhejiang Hospital of Traditional Chinese MedicineZhejiang Chinese Medical UniversityHangzhouChina
  2. 2.College of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhouChina
  3. 3.Hangzhou Red Cross HospitalZhejiang Chinese Medical UniversityHangzhouChina
  4. 4.School of Life Sciences & TechnologyShanghai Jiaotong UniversityShanghaiChina

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