Halogen-substituted derivatives of Dictyostelium differentiation-inducing factor-1 suppress serum-induced cell migration of human breast cancer MDA-MB-231 cells in vitro

Kyoko Totsuka, Yuka Makioka, Kyoichi Iizumi, Katsunori Takahashi, Yoshiteru Oshima, Haruhisa Kikuchi, Yuzuru Kubohara

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Triple-negative breast cancer (TNBC) is highly proliferative and metastatic, and because it lacks three major molecular targets for chemotherapy (estrogen receptor, progesterone receptor, and human epidermal receptor 2), it is extremely refractory. Differentiation-inducing factor 1 (DIF-1) and DIF-3, which are chlorinated alkylphenones, are lead anticancer compounds found in the cellular slime mold Dictyostelium discoideum. Here, we examined the in vitro effects of DIF-1, DIF-3, and 25 DIF derivatives on cell proliferation and serum-induced cell migration in human MDA-MB-231 cells, a model TNBC cell line. We found that Br-DIF-1, a chlorine-to-bromine-substituted derivative of DIF-1, strongly suppressed cell migration (IC50, 3.8 µM) with negligible effects on cell proliferation (IC50, >20 µM). We then synthesized 18 derivatives of Br-DIF-1 and examined the in vitro effects of these derivatives on cell proliferation and serum-induced cell migration in MDA-MB-231 cells. Among the derivatives, Br-DIF-1(+1), Br-DIF-1(+2), and Br-DIF-3(+2) exhibited strong anti-cell migration activities with IC50 values of 1.5, 1.0, and 3.1 µM, respectively, without affecting cell proliferation (IC50, >20 µM). These results suggest that these Br-DIF derivatives are good lead compounds for the development of anti-metastatic drugs against TNBC.

Original languageEnglish
Article number256
JournalBiomolecules
Volume9
Issue number7
DOIs
Publication statusPublished - 2019 Jul

Keywords

  • Anticancer drug
  • Cell migration
  • DIF
  • Dictyostelium discoideum
  • Metastasis
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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