ArticleInternational journal of molecular sciences2023
Cyclophilin A Inhibitors Suppress Proliferation and Induce Apoptosis of MKN45 Gastric Cancer Stem-like Cells by Regulating CypA/CD147-Mediated Signaling Pathway.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Molecular targets and mechanisms of traditional Chinese medicine combined with chemotherapy for gastric cancer: a meta-analysis and multi-omics approach.Annals of medicine · 2025Pooled it
- Bufalin Suppresses Triple-Negative Breast Cancer Stem Cell Growth by Inhibiting the Wnt/β-Catenin Signaling Pathway.Journal of microbiology and biotechnology · 2025Article
- CD147-high extracellular vesicles promote gastric cancer metastasis via VEGF/AKT/eNOS and AKT/mTOR pathways.Oncogenesis · 2025Article
- Harnessing Natural Products to Surmount Drug Resistance in Gastric Cancer: Mechanisms and Therapeutic Perspectives.International journal of biological sciences · 2025Review
- Article
- Hotspots and trends in gastric cancer stem cell research: a visualization and bibliometric analysis.Frontiers in oncology · 2025Review
- Cyclophilin A knockdown inhibits the proliferation and metastatic ability of AGS gastric cancer stem cells by downregulating CD147/STAT3/AKT/ERK and epithelial‑mesenchymal transition.Molecular medicine reports · 2025Article
- Unveiling the impact of CD133 on cell cycle regulation in radio- and chemo-resistance of cancer stem cells.Frontiers in public health · 2025Review
- Cyclophilin A: promising target in cancer therapy.Cancer biology & therapy · 2024Review
- The effects of CypA on apoptosis: potential target for the treatment of diseases.Applied microbiology and biotechnology · 2024Review
- Article
- The role of the SOX2 gene in cervical cancer: focus on ferroptosis and construction of a predictive model.Journal of cancer research and clinical oncology · 2024Article
- Article
- Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers.Molecules (Basel, Switzerland) · 2024Review
- Inhibition of PRMT1 Suppresses the Growth of U87MG-Derived Glioblastoma Stem Cells by Blocking the STAT3 Signaling Pathway.International journal of molecular sciences · 2024Article
- Article
- Bufotalin Suppresses Proliferation and Metastasis of Triple-Negative Breast Cancer Cells by Promoting Apoptosis and Inhibiting the STAT3/EMT Axis.Molecules (Basel, Switzerland) · 2023Article
- Natural Cyclophilin A Inhibitors Suppress the Growth of Cancer Stem Cells in Non-Small Cell Lung Cancer by Disrupting Crosstalk between CypA/CD147 and EGFR.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Gastric cancer stem cells (GCSCs) are a subgroup of gastric cancer (GC) cells with high self-renewal and multi-lineage differentiation abilities that lead to tumor initiation, metastasis, drug resistance, and tumor relapse. Therefore, the eradication of GCSCs can contribute to the effective treatment of advanced or metastatic GC. In our previous study, compound 9 (C9), a novel derivative of nargenicin A1, was identified as a potential natural anticancer agent that specifically targeted cyclophilin A (CypA). However, its therapeutic effect and molecular mechanisms of action on GCSC growth have not been assessed. In this study, we investigated the effects of natural CypA inhibitors, including C9 and cyclosporin A (CsA), on the growth of MKN45-derived GCSCs. Compound 9 and CsA effectively suppressed cell proliferation by inducing cell cycle arrest at the G0/G1 phase and promoted apoptosis by activating the caspase cascade in MKN45 GCSCs. In addition, C9 and CsA potently inhibited tumor growth in the MKN45 GCSC-grafted chick embryo chorioallantoic membrane (CAM) model. Furthermore, the two compounds significantly decreased the protein expression of key GCSC markers including CD133, CD44, integrin α6, Sox2, Oct4, and Nanog. Notably, the anticancer activities of C9 and CsA in MKN45 GCSCs were associated with the regulation of CypA/CD147-mediated AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Collectively, our findings suggest that the natural CypA inhibitors C9 and CsA could be novel anticancer agents used to combat GCSCs by targeting the CypA/CD147 axis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.