ArticleBMC cancer2019
Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- S6K1 Modulates STAT3 Activation to Promote Resistance to Radiotherapy in Lung Cancer.International journal of molecular sciences · 2026Article
- S6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.International journal of biological sciences · 2025Article
- Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity.Biomolecules · 2024Review
- ELK1/MTOR/S6K1 Pathway Contributes to Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Article
- ULK1 Mediated Autophagy-Promoting Effects of Rutin-Loaded Chitosan Nanoparticles Contribute to the Activation of NF-κB Signaling Besides Inhibiting EMT in Hep3B Hepatoma Cells.International journal of nanomedicine · 2024Article
- Development of 6-amido-4-aminoisoindolyn-1,3-diones as p70S6K1 inhibitors and potential breast cancer therapeutics.Frontiers in molecular biosciences · 2024Article
- Anti-pulmonary fibrosis activity analysis of methyl rosmarinate obtained fromFrontiers in pharmacology · 2024Article
- Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives.Biomolecules & therapeutics · 2024Review
- Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases.Nutrients · 2023Review
- The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics.International journal of molecular sciences · 2023Review
- Integration of phytotherapy and chemotherapy: Recent advances in anticancer molecular pathways.Iranian journal of basic medical sciences · 2023Review
- Journey of Rosmarinic Acid as Biomedicine to Nano-Biomedicine for Treating Cancer: Current Strategies and Future Perspectives.Pharmaceutics · 2022Review
- Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer.Biomolecules · 2022Review
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Repurposing Tranexamic Acid as an Anticancer Agent.Frontiers in pharmacology · 2021Article
- Healthful aging mediated by inhibition of oxidative stress.Ageing research reviews · 2020Review
- Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1.Pharmaceuticals (Basel, Switzerland) · 2020Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe mTOR/S6K1 signaling pathway is often activated in cervical cancer, and thus considered a molecular target for cervical cancer therapies. Inhibiting mTOR is cytotoxic to cervical cancer cells and creates a synergistic anti-tumor effect with conventional chemotherapy agents. In this study, we identified a novel S6K1 inhibitor, rosmarinic acid methyl ester (RAME) for the use of therapeutic agent against cervical cancer.
methodsCombined structure- and ligand-based virtual screening was employed to identify novel S6K1 inhibitors among the in house natural product library. In vitro kinase assay and immunoblot assay was used to examine the effects of RAME on S6K1 signaling pathway. Lipidation of LC3 and mRNA levels of ATG genes were observed to investigate RAME-mediated autophagy. PARP cleavage, mRNA levels of apoptotic genes, and cell survival was measured to examine RAME-mediated apoptosis.
resultsRAME was identified as a novel S6K1 inhibitor through the virtual screening. RAME, not rosmarinic acid, effectively reduced mTOR-mediated S6K1 activation and the kinase activity of S6K1 by blocking the interaction between S6K1 and mTOR. Treatment of cervical cancer cells with RAME promoted autophagy and apoptosis, decreasing cell survival rate. Furthermore, we observed that combination treatment with RAME and cisplatin greatly enhanced the anti-tumor effect in cisplatin-resistant cervical cancer cells, which was likely due to mTOR/S6K1 inhibition-mediated autophagy and apoptosis.
conclusionsOur findings suggest that inhibition of S6K1 by RAME can induce autophagy and apoptosis in cervical cancer cells, and provide a potential option for cervical cancer treatment, particularly when combined with cisplatin.
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