Related Experiment Video
Updated: Mar 23, 2026
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Da0324, an inhibitor of nuclear factor-κB activation, demonstrates selective antitumor activity on human gastric
Rong Jin1, Yiqun Xia2, Qiuxiang Chen2
1Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China; Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Background:
The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells.
Methods:
The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay.
Results:
High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation and invasion, arrested the cell cycle, and induced apoptosis in vitro.
Conclusion:
The asymmetric mono-carbonyl analog of curcumin Da0324 exhibited significantly improved antigastric cancer activity. Da0324 may be a promising NF-κB inhibitor for the selective targeting of cancer cells. However, further studies are needed in animals to validate these findings for the therapeutic use of Da0324.
Insights
A novel curcumin analog, Da0324, effectively inhibits nuclear factor-κB (NF-κB) in gastric cancer cells, showing potent antitumor activity and improved stability. This compound presents a promising therapeutic strategy for gastric cancer by selectively targeting cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Nuclear factor-κB (NF-κB) is constitutively activated in various human cancers, including gastric cancer.
- NF-κB inhibitors that selectively kill cancer cells are crucial for effective cancer treatment.
- Curcumin, a known NF-κB inhibitor, has limitations due to low potency and poor bioavailability.
Purpose of the Study:
- To investigate the expression of NF-κB in gastric cancer.
- To evaluate the antitumor activity and mechanism of the novel NF-κB inhibitor Da0324 on human gastric cancer cells.
Main Methods:
- NF-κB expression was assessed using Western blot in gastric cancer and normal tissues/cells.
- Cell viability was determined using the MTT assay across multiple gastric cancer cell lines and a normal cell line.
- In vitro stability of Da0324 was evaluated using absorption spectrum and HPLC methods.
- NF-κB activation, proliferation, invasion, cell cycle, and apoptosis were analyzed using Western blot, immunofluorescence, and other assays.
Main Results:
- Elevated p65 levels were observed in gastric cancer tissues and cells.
- Da0324 demonstrated significant growth inhibition in gastric cancer cell lines with low toxicity to normal cells.
- Da0324 exhibited enhanced in vitro stability compared to curcumin.
- Da0324 effectively blocked NF-κB activation, inhibited tumor proliferation and invasion, induced cell cycle arrest, and promoted apoptosis.
Conclusions:
- The novel curcumin analog Da0324 shows enhanced anti-gastric cancer activity and improved stability.
- Da0324 holds promise as a selective NF-κB inhibitor for targeting cancer cells.
- Further in vivo studies are warranted to validate Da0324's therapeutic potential in gastric cancer.
More Related Videos
06:00Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
10:28Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
02:34Inhibition of CDK Activity
02:34Inhibition of Cdk Activity
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists