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Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways.
Exp Hematol. 2010 Mar; 38(3):191-201.EH

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)-kappaB 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-kappaB activator IkappaB kinase alpha/beta. 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.

Authors+Show Affiliations

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20045442

Citation

Zhang, Yi-Wen, et al. "Eriocalyxin B Induces Apoptosis in Lymphoma Cells Through Multiple Cellular Signaling Pathways." Experimental Hematology, vol. 38, no. 3, 2010, pp. 191-201.
Zhang YW, Jiang XX, Chen QS, et al. Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways. Exp Hematol. 2010;38(3):191-201.
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
Zhang YW, et al. Eriocalyxin B Induces Apoptosis in Lymphoma Cells Through Multiple Cellular Signaling Pathways. Exp Hematol. 2010;38(3):191-201. PubMed PMID: 20045442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways. AU - Zhang,Yi-Wen, AU - Jiang,Xiao-Xing, AU - Chen,Qiu-Sheng, AU - Shi,Wen-Yu, AU - Wang,Lan, AU - Sun,Han-Dong, AU - Shen,Zhi-Xiang, AU - Chen,Zhu, AU - Chen,Sai-Juan, AU - Zhao,Wei-Li, Y1 - 2010/01/04/ PY - 2009/08/07/received PY - 2009/12/07/revised PY - 2009/12/22/accepted PY - 2010/1/5/entrez PY - 2010/1/5/pubmed PY - 2010/4/24/medline SP - 191 EP - 201 JF - Experimental hematology JO - Exp Hematol VL - 38 IS - 3 N2 - 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)-kappaB 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-kappaB activator IkappaB kinase alpha/beta. 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. SN - 1873-2399 UR - https://www.unboundmedicine.com/medline/citation/20045442/Eriocalyxin_B_induces_apoptosis_in_lymphoma_cells_through_multiple_cellular_signaling_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-472X(09)00486-X DB - PRIME DP - Unbound Medicine ER -