Absolute Configuration Of Tetrandrine And Isotetrandrine Influences Their Anti-Proliferation Effects In Human T Cells Via Different Regulation Of Nf-Kappa B

Natural compound tetrandrine was reported to inhibit the proliferation of T cells by inhibiting activation of NF-kappa B. 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-kappa B. 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 mu M, 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 mu M, 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 mu M of isotetrandrine largely decreased the expression of p-NF-kappa B and NF-kappa B in both MOLT-4 and MOLT-4/DNR T cells (p < 0.05), whereas 10 mu M of tetrandrine slightly inhibited the phosphorylation of p-NF-kappa B with little influence on the expression of NF-kappa B. 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-kappa B.