RRC ID 60049
著者 Yu B, Yuan B, Kiyomi A, Kikuchi H, Hayashi H, Hu X, Okazaki M, Sugiura M, Hirano T, Pei X, Takagi N.
タイトル Differentiation induction of human breast cancer cells by arsenite in combination with tetrandrine.
ジャーナル Am J Transl Res
Abstract BACKGROUND:To provide novel insight into the development of new therapeutic strategies to combat breast cancer, differentiation-inducing activity of clinically achievable concentrations of arsenite (AsIII) and tetrandrine (Tetra) was investigated in breast cancer cell lines MDA-MB-231 and MCF-7.
METHODS:Differentiation induction of cancer cells was analyzed by flow cytometer. Alterations of genes related to differentiation, and proliferation of human normal peripheral blood mononuclear cells (PBMCs) were analyzed using western blotting and cell viability assay, respectively.
RESULTS:Exposure to Tetra alone or in combination with AsIII induced differentiation of both cells characterized by upregulation of ICAM-1, downregulation of Her2/neu. In comparison with MCF-7, the combination of lower concentrations of AsIII and Tetra induced differentiation of MDA-MB-231, indicating that MDA-MB-231 cells were highly susceptible to differentiation. The differentiation occurred in parallel with activation of Erk signaling pathway, and was abolished by PD98059, a potent Erk inhibitor. Consistent with in vitro experimental results, the upregulation of ICAM-1 and the activation of Erk signaling pathway were also observed in MDA-MB-231 breast tumors in xenograft mouse obtained from our previous study. No obvious proliferation inhibition of PBMCs was observed following the exposure to AsIII combined with Tetra at the concentrations capable of inducing differentiation of MDA-MB-231 cells.
CONCLUSION:The Erk signaling pathway may be crucially involved in the differentiation induction of breast cancer cells in vitro and in vivo. Collectively, our results suggest that the combination can probably serve as promising candidates for the development of novel therapeutic approaches for different types of breast cancer.
巻・号 11(12)
ページ 7310-7323
公開日 2019-1-1
PMID 31934280
PMC PMC6943472
IF 3.266
引用数 2
リソース情報
ヒト・動物細胞 MCF7(RCB1904)