Methylprednisolone potentiates tetrandrine pharmacodynamics against human T lymphoblastoid leukemia MOLT-4 cells via regulation of NF-κB activation and cell cycle transition

Abstract

Low response to glucocorticoid (GC) predicts therapeutic failure in acute T lymphoblastic leukemia (T-ALL). The efficient and safe strategies are still required for the treatment of relapsed T-ALL. Our previous study revealed that tetrandrine induces apoptosis in human T lymphoblastoid leukemia cells possibly via activation of NF-κB. GCs are recognized as typical NF-κB inhibitors and are used for the treatment of T-ALL patients. In the present study, we examined whether methylprednisolone (MP) potentiates the cytotoxic effect of tetrandrine (TET) via NF-κB regulation by using human T lymphoblastoid leukemia MOLT-4 cells. WST-8 assay data showed that nM grade of MP increased cytotoxicity of TET against MOLT-4 cells in vitro. This effect seemed to be related to the potentiation of TET action by MP to induce apoptosis. Meanwhile, the combination also impeded the transition of cell cycle from G0/G1 phase to S phase. However, the regulation effect of this combination on cell cycle had no relationship with cyclin signaling pathway, since the drug-combination did not influence on the expression of cyclin A2/B1/D1 in MOLT-4 cells. On the other hand, the combination significantly inhibited the phosphorylation of NF-κB (p < 0.01). These results suggest that nM grade of MP potentiates the cytotoxic effect of TET possibly via regulation of NF-κB activation and “G0/G1 to S” phase transition in human T lymphoblastoid leukemia MOLT-4 cells. Combination of TET and MP may provide a new therapeutic strategy for relapsed T-ALL.