TY - JOUR
T1 - Halogen-substituted derivatives of Dictyostelium differentiation-inducing factor-1 suppress serum-induced cell migration of human breast cancer MDA-MB-231 cells in vitro
AU - Totsuka, Kyoko
AU - Makioka, Yuka
AU - Iizumi, Kyoichi
AU - Takahashi, Katsunori
AU - Oshima, Yoshiteru
AU - Kikuchi, Haruhisa
AU - Kubohara, Yuzuru
N1 - Funding Information:
Funding: This work was supported in part by JSPS KAKENHI Grants (no. 15K07964 to YK and YO) and by the Joint Research Program of Juntendo University, Faculty of Health and Sports Science (to YK).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Anticancer drug
KW - Cell migration
KW - DIF
KW - Dictyostelium discoideum
KW - Metastasis
KW - Triple-negative breast cancer
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U2 - 10.3390/biom9070256
DO - 10.3390/biom9070256
M3 - Article
C2 - 31261818
AN - SCOPUS:85069262582
VL - 9
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 7
M1 - 256
ER -