Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways

Yi Wen Zhang, Xiao Xing Jiang, Qiu Sheng Chen, Wen Yu Shi, Lan Wang, Han Dong Sun, Zhi Xiang Shen, Zhu Chen, Sai Juan Chen, Wei Li Zhao

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Objective: Eriocalyxin B (EriB) is a natural diterpenoid purified from Isodon eriocalyx var. laxiflora and possesses strong antileukemic activity. In this study, we further investigated its effect and mechanism of action in human lymphoma. Materials and Methods: In vitro, a series of B- and T-lymphoma cells were treated with EriB. Cell apoptosis was analyzed using flow cytometric assay. Expression of proteins related to apoptosis and cell signal transduction were assessed using Western blot. In vivo antitumor activity of EriB was examined in murine xenograft B- and T-lymphoma models, with in situ cell apoptosis detected by terminal deoxytransferase-catalyzed DNA nick-end labeling assay. Results: EriB significantly inhibited lymphoma cell proliferation and induced apoptosis in association with caspase activation. Antiapoptotic Bcl-2 family members Bcl-2 and Bcl-xL were downregulated, with proapoptotic member Bax stable or upregulated, resulting in reduced Bcl-2/Bax and Bcl-xL/Bax ratios. Meanwhile, multiple signal transduction pathways were involved in lymphoma cell apoptosis in response to EriB, including inhibition of nuclear factor (NF)-κB and AKT pathways, and the activation of extracellular signal-related kinase (ERK) pathway. AKT inactivation was related to increased expression of cyclin-dependent kinase inhibitor P21, decreased expression of antiapoptotic phosphorylated form of Bad, and NF-κB activator IκB kinase α/β. ERK activation corresponded to reactive oxygen species production and could be blocked by antioxidant dithiothreitol. In murine xenograft lymphoma models, EriB remarkably inhibited tumor growth and induced in situ tumor cell apoptosis. Conclusion: These findings broaden the value of EriB as a promising candidate targeting apoptosis cascade in treatment of hematological malignancies.

Original languageEnglish (US)
Pages (from-to)191-201
Number of pages11
JournalExperimental Hematology
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Zhang, Y. W., Jiang, X. X., Chen, Q. S., Shi, W. Y., Wang, L., Sun, H. D., Shen, Z. X., Chen, Z., Chen, S. J., & Zhao, W. L. (2010). Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways. Experimental Hematology, 38(3), 191-201. https://doi.org/10.1016/j.exphem.2009.12.005