ArticleMolecular biology reports2022
PIK3CA hotspot mutations p. H1047R and p. H1047L sensitize breast cancer cells to thymoquinone treatment by regulating the PI3K/Akt1 pathway.
Article in Molecular biology reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- Thymoquinone Enhances Tamoxifen Efficacy Against Triple-Negative Breast Cancer by Targeting EMT Signaling.International journal of breast cancer · 2026Article
- Colorectal Cancer Cells-Derived Exosomal PIK3CA Mutation DNA Promotes Tumor Metastasis by Activating Fibroblast and Affecting Tumor Metastatic Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Vertical inhibition of p110α/AKT and N-cadherin enhances treatment efficacy in PIK3CA-aberrated ovarian cancer cells.Molecular oncology · 2025Article
- Exploring breast cancer associated-gene panel for next-generation sequencing and identifying new, pathogenic variants in breast cancer from western China.Journal of Cancer · 2025Article
- Comprehensive analysis, diagnosis, prognosis, and cordycepin (CD) regulations for GSDME expressions in pan-cancers.Cancer cell international · 2024Article
- Prevalence and effect ofSaudi journal of biological sciences · 2024Article
- Mutational Landscape and In-Silico Analysis ofACS omega · 2023Article
- Novel pathogenic3 Biotech · 2023Article
- Comprehensive analysis, immune, and cordycepin regulation for SOX9 expression in pan-cancers and the matched healthy tissues.Frontiers in immunology · 2023Article
- Antiviral Potential of Small Molecules Cordycepin, Thymoquinone, and N6, N6-Dimethyladenosine Targeting SARS-CoV-2 Entry Protein ADAM17.Molecules (Basel, Switzerland) · 2022Article
- HSPA6 and its role in cancers and other diseases.Molecular biology reports · 2022Review
- Impact ofMolecules (Basel, Switzerland) · 2022Article
- Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis.Cellular & molecular biology letters · 2022Review
- Clinical Response to PI3K-α Inhibition in a Cohort of Children and Adults WithJournal of vascular anomalies · 2022Article
- Anticancer Effect of Spices Used in Mediterranean Diet: Preventive and Therapeutic Potentials.Frontiers in nutrition · 2022Review
- COVID-19 receptor and malignant cancers: Association ofInternational journal of biological sciences · 2022Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
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Abstract
backgroundNigella sativa (N. sativa) exhibits anti-inflammatory, antioxidant, antidiabetic, antimetastatic and antinociceptive effects and has been used to treat dozens of diseases. Thymoquinone (TQ) is an important and active component isolated from N. sativa seeds. Inhibition of cancer-associated activating PIK3CA mutations is a new prospective targeted therapy in personalized metastatic breast cancer (MBC). TQ is reported to be an effective inhibitor of the PI3K/Akt1 pathway in MBC. This study aimed to evaluate the in vitro antitumor effect of TQ in the context of two PIK3CA hotspot mutations, p. H1047R and p. H1047L. METHODS AND
resultsMolecular dynamics, free energy landscapes and principal component analyses were also used to survey the mechanistic effects of the p. H1047R and p. H1047L mutations on the PI3K/Akt1 pathway. Our findings clearly confirmed that the p. H1047R and p. H1047L mutants could reduce the inhibitory effect of ΔNp63α on the kinase domain of PIK3CA, resulting in increased activity of PI3K downstream signals. Structurally, the partial disruption of the interaction between the ΔNp63α DNA binding domain and the PIK3CA kinase domain at residues 114-359 and 797-1068 destabilizes the conformation of the activation loop and modifies the PIK3CA/ΔNp63α complex. Alongside these structural changes, we found that TQ treatment resulted in high PI3K/Akt1 pathway inhibition in p. H1047R and p. H1047L-expressing cells versus wild-type cells.
conclusionsThese two PIK3CA hotspot mutations therefore not only contribute to tumor progression in patients with MBC but may also serve as targets for the development of novel small molecule therapeutic strategies.
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