姜黄素已被证明具有抗肿瘤特性，但其效力和生物利用度低限制了其临床应用。我们设计了一种新型姜黄素[1-丙基-3,5-双(2-溴亚苄基)-4-哌啶酮](PBPD)，它具有更高的抗肿瘤强度并提高了生物利用度。使用Cell counting kit-8检测细胞活性。 Transwell实验检测细胞侵袭和迁移能力。 Western blot和定量聚合酶链反应用于检测蛋白质水平及其信使RNA表达。使用免疫荧光检测蛋白质位置。 PBPD显着抑制宫颈癌细胞的增殖，Hela细胞的IC50值为4.16μM，SiHa细胞的IC50值为3.78μM，从而诱导铜凋亡。转录组测序分析显示，PBPD 显着抑制 Notch1/免疫球蛋白 kappa J 区重组信号结合蛋白 (RBP-J) 和核因子红细胞 2 相关因子 2 (NRF2) 信号通路，同时上调铁氧还蛋白 1 (FDX1) 表达。敲除Notch1或RBP-J可显着抑制NRF2表达并上调FDX1表达，从而抑制烟酰胺腺嘌呤二核苷酸磷酸活性并诱导氧化应激，进而激活内质网应激并诱导细胞死亡。 Notch1或RBP-J的过表达导致NRF2启动子区域内RBP-J的富集，从而刺激NRF2转录。 NRF2 敲除导致 FDX1 表达增加，导致铜凋亡。此外，PBPD通过抑制肿瘤微环境酸化、降低细胞代谢来抑制宫颈癌细胞的侵袭和迁移。总之，PBPD 显着抑制宫颈癌细胞的增殖、侵袭和迁移，可能成为治疗宫颈癌的新型潜在候选药物。© 2024 Wiley periodicals LLC。

Curcumin has been shown to have antitumor properties, but its low potency and bioavailability has limited its clinical application. We designed a novel curcuminoid, [1-propyl-3,5-bis(2-bromobenzylidene)-4-piperidinone] (PBPD), which has higher antitumor strength and improves bioavailability. Cell counting kit-8 was used to detect cell activity. Transwell assay was used to detect cell invasion and migration ability. Western blot and quantitative polymerase chain reaction were used to detect protein levels and their messenger RNA expression. Immunofluorescence was used to detect the protein location. PBPD significantly inhibited the proliferation of cervical cancer cells, with an IC50 value of 4.16 μM for Hela cells and 3.78 μM for SiHa cells, leading to the induction of cuproptosis. Transcriptome sequencing analysis revealed that PBPD significantly inhibited the Notch1/Recombination Signal Binding Protein for Immunoglobulin kappa J Region (RBP-J) and nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathways while upregulating ferredoxin 1 (FDX1) expression. Knockdown of Notch1 or RBP-J significantly inhibited NRF2 expression and upregulated FDX1 expression, leading to the inhibition of nicotinamide adenine dinucleotide phosphate activity and the induction of oxidative stress, which in turn activated endoplasmic reticulum stress and induced cell death. The overexpression of Notch1 or RBP-J resulted in the enrichment of RBP-J within the NRF2 promoter region, thereby stimulating NRF2 transcription. NRF2 knockdown resulted in increase in FDX1 expression, leading to cuproptosis. In addition, PBPD inhibited the acidification of tumor niche and reduced cell metabolism to inhibit cervical cancer cell invasion and migration. In conclusion, PBPD significantly inhibits the proliferation, invasion, and migration of cervical cancer cells and may be a novel potential drug candidate for treatment of cervical cancer.© 2024 Wiley Periodicals LLC.