A Curcumin Analog, 3,5-Bis(2′-ethoxybenzylidene)-piperidine-4-one (E145), Suppresses NF-κB Signaling to Inhibit Breast Cancer Growth and Metastasis
Abstract
Curcumin is a naturally occurring bioactive compound with well-characterized anti-inflammatory and antitumor properties; however, its clinical utility is limited by poor bioavailability and chemical instability. To overcome these limitations, various curcumin analogs have been developed. In this study, we investigated the antitumor and antimetastatic effects of 3,5-bis(2'-ethoxybenzylidene)-piperidine-4-one (E145), a monocarbonyl curcumin analog, with a particular focus on its ability to inhibit nuclear factor-kappaB (NF-κB) signaling in breast cancer cells. We first evaluated the effects of E145 on cell proliferation in murine 4T1 and human MDA-MB-231 breast cancer cell lines. E145 inhibited cell proliferation in a dose-dependent manner and suppressed phosphorylation of the NF-κB p65 subunit. Furthermore, E145 blocked tumor necrosis factor alpha-induced NF-κB activation by inhibiting both p65 phosphorylation and nuclear translocation. Consistently, E145 reduced the expression of NF-κB-regulated pro-tumorigenic factors, including vascular endothelial growth factor, matrix metalloproteinase-9, interleukin-1β (IL-1β), and IL-6. Functional assays demonstrated that E145 markedly suppressed the migration and invasion of breast cancer cells in vitro. In addition, experimental lung metastasis assays revealed that E145 treatment significantly reduced metastatic colonization of 4T1 cells in vivo. Collectively, these findings indicate that E145 exerts potent antimetastatic effects by inhibiting cell-intrinsic NF-κB activation and downstream inflammatory mediators. These results suggest that E145 is a promising therapeutic candidate for targeting NF-κB-driven breast cancer progression and metastasis.
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BibTeX
@article{jabbar2026curcumin,
title = {{A Curcumin Analog, 3,5-Bis(2′-ethoxybenzylidene)-piperidine-4-one (E145), Suppresses NF-κB Signaling to Inhibit Breast Cancer Growth and Metastasis}},
author = {Sana Jabbar and Yue Zhou and Seiya Kobayashi and Ka He and Sisca Ucche and Ritmaleni and So-Ichiro Sasaki and Yoshihiro Hayakawa},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = jul,
doi = {10.1248/bpb.b26-00307},
url = {https://www.jstage.jst.go.jp/article/bpb/49/7/49_b26-00307/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - A Curcumin Analog, 3,5-Bis(2′-ethoxybenzylidene)-piperidine-4-one (E145), Suppresses NF-κB Signaling to Inhibit Breast Cancer Growth and Metastasis
AU - Sana Jabbar
AU - Yue Zhou
AU - Seiya Kobayashi
AU - Ka He
AU - Sisca Ucche
AU - Ritmaleni
AU - So-Ichiro Sasaki
AU - Yoshihiro Hayakawa
PY - 2026
DA - 2026/07/28
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b26-00307
UR - https://www.jstage.jst.go.jp/article/bpb/49/7/49_b26-00307/_article
AB - Curcumin is a naturally occurring bioactive compound with well-characterized anti-inflammatory and antitumor properties; however, its clinical utility is limited by poor bioavailability and chemical instability. To overcome these limitations, various curcumin analogs have been developed. In this study, we investigated the antitumor and antimetastatic effects of 3,5-bis(2'-ethoxybenzylidene)-piperidine-4-one (E145), a monocarbonyl curcumin analog, with a particular focus on its ability to inhibit nuclear factor-kappaB (NF-κB) signaling in breast cancer cells. We first evaluated the effects of E145 on cell proliferation in murine 4T1 and human MDA-MB-231 breast cancer cell lines. E145 inhibited cell proliferation in a dose-dependent manner and suppressed phosphorylation of the NF-κB p65 subunit. Furthermore, E145 blocked tumor necrosis factor alpha-induced NF-κB activation by inhibiting both p65 phosphorylation and nuclear translocation. Consistently, E145 reduced the expression of NF-κB-regulated pro-tumorigenic factors, including vascular endothelial growth factor, matrix metalloproteinase-9, interleukin-1β (IL-1β), and IL-6. Functional assays demonstrated that E145 markedly suppressed the migration and invasion of breast cancer cells in vitro. In addition, experimental lung metastasis assays revealed that E145 treatment significantly reduced metastatic colonization of 4T1 cells in vivo. Collectively, these findings indicate that E145 exerts potent antimetastatic effects by inhibiting cell-intrinsic NF-κB activation and downstream inflammatory mediators. These results suggest that E145 is a promising therapeutic candidate for targeting NF-κB-driven breast cancer progression and metastasis.
SN - 1347-5215
SN - 0918-6158
ER -