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Absolute configuration of tetrandrine and isotetrandrine influences their anti-proliferation effects in human T cells via different regulation of NF-κB

  • Wencheng Xu ORCID logo , Junichi Kusano , Shuhe Chen , Ryusei Yamamoto , Hiroto Matsuda , Yoshikazu Hara , Yoshiaki Fujii , Seiichi Hayashi , Sachiko Tanaka , Kentaro Sugiyama ORCID logo EMAIL logo , Haruki Yamada and Toshihiko Hirano
Published/Copyright: October 30, 2020
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Abstract

Natural compound tetrandrine was reported to inhibit the proliferation of T cells by inhibiting activation of NF-κB. Chemically, isotetrandrine differs from tetrandrine only in the stereochemistry at the chiral centers. The present study aimed to compare their anti-proliferation effects on human T cells with a focus on NF-κB. The IC50 values of tetrandrine against MOLT-4 cells, MOLT-4/DNR cells, and concanavalin A-activated peripheral blood mononuclear cells of healthy subjects and dialysis patients were 4.43 ± 0.22, 3.62 ± 0.22, 1.91 ± 0.22 and 3.03 ± 0.28 μM, respectively. Whereas, the IC50 values of isotetrandrine against the above immune cells were 2.19 ± 0.27, 2.28 ± 0.33, 1.29 ± 0.14 and 1.55 ± 0.26 μM, respectively. The inhibitory effect of isotetrandrine against the proliferation of T cells was stronger than that of tetrandrine significantly (p < 0.05). Molecular mechanism investigation showed that 10 μM of isotetrandrine largely decreased the expression of p-NF-κB and NF-κB in both MOLT-4 and MOLT-4/DNR T cells (p < 0.05), whereas 10 μM of tetrandrine slightly inhibited the phosphorylation of p-NF-κB with little influence on the expression of NF-κB. Taken together, absolute configurations of tetrandrine and isotetrandrine are suggested to influence on their anti-proliferation effects in human T cells via different regulation of NF-κB.


Corresponding author: Kentaro Sugiyama, Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji city, Tokyo192-0392, Japan, E-mail:

Wencheng Xu, Junichi Kusano: These authors contributed equally to this work.


Funding source: State Scholarship Fund of China Scholarship Council

Award Identifier / Grant number: 201808420024

Funding source: Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan

Award Identifier / Grant number: 15K08081

Funding source: Japan China Sasakawa Medical Fellowship

Award Identifier / Grant number: 2017816

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan under Grant (15K08081); Japan China Sasakawa Medical Fellowship under Grant (2017816) and State Scholarship Fund of China Scholarship Council under Grant (201808420024).

  3. Competing interests: The authors declare no conflicts of interest regarding this article.

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Received: 2020-03-23
Accepted: 2020-06-13
Published Online: 2020-10-30
Published in Print: 2021-01-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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