Related Experiment Video
Updated: Jan 20, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Identification of New Mono/Dihydroxynaphthoquinone as Lead Agents That Inhibit the Growth of Refractive and
Richard Schroeder1, Mary Sfondouris2, Navneet Goyal1
1Department of Chemistry, Xavier University of Louisiana, 1, Drexel Dr., New Orleans, Louisiana 70125, United States.
Abstract:
Human epidermal growth factor receptor 2 (HER2) is overexpressed in nearly 20-30% of breast cancers and is associated with metastasis resulting in poor patient survival and high recurrence. The dual EGFR/HER2 kinase inhibitor lapatinib has shown promising clinical results, but its limitations have also led to the resistance and activation of tumor survival pathways. Following our previous investigation of quinones as HER2 kinase inhibitors, we synthesized several naphthoquinone derivatives that significantly inhibited breast tumor cells expressing HER2 and trastuzumab-resistant HER2 oncogenic isoform, HER2Δ16. Two of these compounds were shown to be more effective than lapatinib at the inhibition of HER2 autophosphorylation of Y1248. Compounds 7 (5,8-dihydroxy-2-methylnaphthalene-1,4-dione) and 9 (2-(bromomethyl)-5,8-dihydroxynaphthalene-1,4-dione) inhibited HER2-expressing MCF-7 cells (IC50 0.29 and 1.76 μM, respectively) and HER2Δ16-expressing MCF-7 cells (IC50 0.51 and 1.76 μM, respectively). Compound 7 was also shown to promote cell death in multiple refractory breast cancer cell lines with IC50 values ranging from 0.12 to 2.92 μM. These compounds can function as lead compounds for the design of a new series of nonquinonoid structural compounds that can maintain a similar inhibition profile.
Insights
New naphthoquinone derivatives show potent inhibition of HER2-positive breast cancer cells, including resistant forms. These compounds offer a promising alternative to existing therapies like lapatinib for HER2-driven cancers.
Area of Science:
- Medicinal Chemistry
- Oncology
- Molecular Biology
Background:
- HER2 overexpression in 20-30% of breast cancers correlates with poor prognosis.
- Lapatinib, a dual EGFR/HER2 inhibitor, faces limitations due to resistance and pathway activation.
- Previous research explored quinones as HER2 kinase inhibitors.
Purpose of the Study:
- To synthesize and evaluate novel naphthoquinone derivatives as HER2 kinase inhibitors.
- To assess the efficacy of these compounds against HER2-overexpressing and trastuzumab-resistant HER2Δ16 breast cancer cells.
- To identify potential lead compounds for new nonquinonoid HER2 inhibitors.
Main Methods:
- Synthesis of naphthoquinone derivatives.
- Inhibition assays for HER2 autophosphorylation (Y1248).
- Cell viability assays (IC50 determination) in HER2-expressing and HER2Δ16-expressing MCF-7 cells, and refractory breast cancer cell lines.
Main Results:
- Two naphthoquinone derivatives, compounds 7 and 9, significantly inhibited HER2-expressing and HER2Δ16-expressing MCF-7 cells.
- Compounds 7 and 9 demonstrated superior inhibition of HER2 autophosphorylation at Y1248 compared to lapatinib.
- Compound 7 exhibited potent cell death induction across multiple refractory breast cancer lines (IC50: 0.12–2.92 μM).
Conclusions:
- Novel naphthoquinone derivatives show significant potential as HER2 kinase inhibitors.
- Compounds 7 and 9 represent promising leads for developing new therapies against HER2-positive and resistant breast cancers.
- These findings pave the way for designing nonquinonoid analogs with similar efficacy.
Related Concept Videos
09:29Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
10:51Mammosphere Formation Assay from Human Breast Cancer Tissues and Cell Lines
12:35Comparison of Three Different Methods for Determining Cell Proliferation in Breast Cancer Cell Lines
06:52Monitoring Breast Cancer Growth and Metastatic Colony Formation in Mice using Bioluminescence
07:01Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors
13:38Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells