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Trichosanthin down-regulated p210Bcr-Abl and enhanced imatinib-induced growth arrest in chronic myelogenous leukemia cell line K562

Cancer Chemotherapy and Pharmacology volume 60, pages 581–587 (2007)Cite this article

Abstract

Purpose

Trichosanthin (TCS), an active component extracted from the root tubers of traditional Chinese medical herb Tian-Hua-Fen of the Cucurbitaceae family, has long been used for medical purpose in China; there is increasing interest in developing TCS as cancer therapeutic agents. The present study was to investigate the growth arrest of K562 cells and its molecular mechanisms, which the drugs induced by TCS and the possible functional interaction of TCS with imatinib (STI571) to K562 cells.

Methods

Trypan blue exclusive staining was used to access the cell growth inhibition; western blot was used to evaluate the p210Bcr-Abl, phosphorylated tyrosine kinase (PTK), and some signaling molecules involving in cell proliferation and apoptosis in K562 cells.

Results

TCS and imatinib inhibited K562 cells at a time- and dose-dependent manners, respectively; TCS down-regulated p210Bcr-Abl at a time- and dose-dependent manners; TCS synergistically enhanced imatinib-induced K562 cell growth arrest and down-regulation of p210Bcr-Abl, PTK activities, procaspase-3, Hsp90,NF-κB and PKC.

Conclusion

The results suggest that TCS not only by itself involves but also synergizes activities of imatinib to induce K562 cell growth arrest, down-regulation of p210Bcr-Abl and its downstream signals and to stimulate the effect of the tyrosine kinase inhibition.

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Acknowledgments

We thank Dr. Zhang Qunhao from Harvard Medical School and Dr. Yang Xiaoyi for their kind discussions. This work was supported by Chinese National Natural Science Foundation (No 30171158, 30472187).

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Affiliations

  1. Institute of Clinical Pharmacology, School of Pharmacy, Fujian Medical University, Fujian, 350004, People’s Republic China

    Kunzhong Zhang, Jianhua Xu, Xiuwang Huang, Lixian Wu, Caixia Wen, Yingying Hu, Yu Su & Zhiqiang Zhang

  2. Fujian Institute of Hemetology, Fujian, 350004, People’s Republic China

    Yuanzhong Chen

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  1. Kunzhong Zhang
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Correspondence to Jianhua Xu.

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Zhang, K., Xu, J., Huang, X. et al. Trichosanthin down-regulated p210Bcr-Abl and enhanced imatinib-induced growth arrest in chronic myelogenous leukemia cell line K562. Cancer Chemother Pharmacol 60, 581–587 (2007). https://doi.org/10.1007/s00280-007-0457-0

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  • DOI: https://doi.org/10.1007/s00280-007-0457-0

Keywords

  • Combination drug therapy
  • Trichosanthin
  • Imatinib
  • Cell growth
  • p210Bcr-Abl
  • Chronic myelogenous leukemia
  • K562 cell line