Synergistic therapeutic effect of diethylstilbestrol and CX-4945 in human acute T-lymphocytic leukemia cells

Biomed Pharmacother. 2018 Feb:98:357-363. doi: 10.1016/j.biopha.2017.12.078. Epub 2017 Dec 27.

Abstract

Human acute T-lymphocytic leukemia (T-ALL) is one of the most commonly diagnosed hematological disorders, and is characterized by poor prognosis and survival rate. Despite the development of new therapeutic approaches, leukemia treatment options remain limited. In this study, we investigated the immunosuppressive and anti-proliferative effects of the synthetic estrogen diethylstilbestrol (DES), both alone and combined with the casein kinase 2 (CK2) inhibitor CX-4945. Our results indicated that DES induced caspase-dependent apoptosis in a human T-ALL cell line (Jurkat cells), while exerting no significant cytotoxicity in normal peripheral blood mononuclear cells (PBMCs). Phytohaemagglutinin and phorbol 12-myristate 13-acetate induced interleukin (IL)-2 production and activation of NF-κB signaling pathways, which were both inhibited by DES. Moreover, DES exerted synergistic effects with CX-4945 on proliferation and IL-2 production in Jurkat cells. Our results demonstrated that DES exerts anti-proliferative and immunosuppressive effects through inhibition of CK2 and the NF-κB signaling pathway in human T-ALL Jurkat cells.

Keywords: CK2; DES; IL-2; Jurkat; NF-κB; T-ALL.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Casein Kinase II / antagonists & inhibitors
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Diethylstilbestrol / pharmacology*
  • Drug Synergism
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • NF-kappa B / metabolism
  • Naphthyridines / pharmacology*
  • Phenazines
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Interleukin-2
  • NF-kappa B
  • Naphthyridines
  • Phenazines
  • Diethylstilbestrol
  • silmitasertib
  • Casein Kinase II