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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.

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

Zeitschrift fur Naturforschung. C, Journal of biosciences (2020-10-30)
Wencheng Xu, Junichi Kusano, Shuhe Chen, Ryusei Yamamoto, Hiroto Matsuda, Yoshikazu Hara, Yoshiaki Fujii, Seiichi Hayashi, Sachiko Tanaka, Kentaro Sugiyama, Haruki Yamada, Toshihiko Hirano
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Tetrandrine, analytical standard, for drug analysis
Sigma-Aldrich
PMA, for use in molecular biology applications, ≥99% (HPLC)