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

Authors
  • Xu, Wencheng1
  • Chen, Shuhe1
  • Wang, Xiaoqin2
  • Wu, Hongguang3
  • Yamada, Haruki3
  • Hirano, Toshihiko4
  • 1 Department of Pharmacy, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, PR China; Institute of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, PR China. , (China)
  • 2 Department of Nephrology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, PR China. , (China)
  • 3 Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. , (Japan)
  • 4 Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: [email protected] , (Iran)
Type
Published Article
Journal
Steroids
Publication Date
Aug 17, 2020
Volume
163
Pages
108714–108714
Identifiers
DOI: 10.1016/j.steroids.2020.108714
PMID: 32818521
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2020 Elsevier Inc. All rights reserved.

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