ArticleInternational journal of molecular sciences2021
Identification of Cyclophilin A as a Potential Anticancer Target of Novel Nargenicin A1 Analog in AGS Gastric Cancer Cells.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 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
- Beauvericin Induces Mitochondrial Apoptosis and Attenuates EMT-Associated Phenotypes and Angiogenic Signaling in Colorectal Cancer CellsJournal of microbiology and biotechnology · 2026Article
- A single-cell atlas reveals the tumorigenesis and microenvironment status of primary tracheobronchial tumors.NPJ precision oncology · 2025Article
- HIF-1α: A Key Factor Mediating Tumor Cells from Digestive System to Evade NK Cell Killing via Activating Metalloproteinases to Hydrolyze MICA/B.Biomolecules · 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
- 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
- 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
- Molecular Target and Action Mechanism of Anti-Cancer Agents.International journal of molecular sciences · 2023Article
- Cyclophilin A Inhibitors Suppress Proliferation and Induce Apoptosis of MKN45 Gastric Cancer Stem-like Cells by Regulating CypA/CD147-Mediated Signaling Pathway.International journal of molecular sciences · 2023Article
- Cystathionine γ-lyase mediates cell proliferation, migration, and invasion of nasopharyngeal carcinoma.Oncogene · 2022Article
- Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy.International journal of molecular sciences · 2022Review
- CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma.International journal of molecular sciences · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.
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