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.
Highlights
Breast cancer is the most common cancer affecting women, accounting for 25% of all cancers in women [1,2]
We found that Br-Differentiation-inducing factor 1 (DIF-1) strongly suppressed serum-induced cell migration (SICM) without markedly affecting cell proliferation
We examined the effects of the DIF derivatives on cell proliferation in the MDA-MB-231 cells (Figure 3D)
Summary
Breast cancer is the most common cancer affecting women, accounting for 25% of all cancers in women [1,2]. Four subtypes of breast cancer categorized by receptor status are i) luminal A (estrogen receptor (ER) positive, progesterone receptor (PR) positive, and human epidermal receptor 2 (HER2) negative), ii) luminal B PR-positive, and HER2-positive), iii) HER2-enriched (ER-negative, PR-negative, and HER2-positive), and iv) triple-negative (ER-negative, PR-negative, and HER2 negative) breast cancer [2] TNBC is highly proliferative and metastatic and because molecular targeted therapies available for the treatment of other breast cancers are unavailable, TNBC is extremely refractory [4,6,7,8,9]. Innovative breast cancer treatments, including the development of novel anticancer and anti-metastasis drugs, are needed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
