ArticleFrontiers in oncology2022
Suppression of head and neck cancer cell survival and cisplatin resistance by GRP78 small molecule inhibitor YUM70.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- The Role of Metallodrugs in Enhancing Neuroendocrine Neoplasm Therapies: The Promising Anticancer Potential of Ruthenium-Based Complexes.Molecules (Basel, Switzerland) · 2025Review
- Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Modulation of Endoplasmic Reticulum Stress in Experimental Anti-Cancer Therapy.International journal of molecular sciences · 2025Review
- Endoplasmic reticulum stress-MMRN1 positive feedback contributes to cisplatin resistance in small cell lung cancer.Journal of thoracic disease · 2024Article
- Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19.Cell & bioscience · 2024Article
- GRP78 inhibitor YUM70 upregulates 4E-BP1 and suppresses c-MYC expression and viability of oncogenic c-MYC tumors.Neoplasia (New York, N.Y.) · 2024Article
- Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.medRxiv : the preprint server for health sciences · 2024Article
- The two-faced role of RNA methyltransferase METTL3 on cellular response to cisplatin in head and neck squamous cell carcinomaFrontiers in oncology · 2024Article
- ER chaperone GRP78/BiP translocates to the nucleus under stress and acts as a transcriptional regulator.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage.Viruses · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. Surgical resection, radiation and chemotherapy are the mainstay of HNSCC treatment but are often unsatisfactory. Cisplatin is a commonly used chemotherapy in HNSCC; however, cisplatin resistance is a major cause of relapse and death. The 78-kD glucose-regulated protein (GRP78) is the master regulator of the unfolded protein response (UPR) and is implicated in therapeutic resistance in cancer. The role of GRP78 in cisplatin resistance in HNSCC remains unclear. YUM70 is a newly discovered hydroxyquinoline analogue and found to be an inhibitor of GRP78. The effect of YUM70 in HNSCC cell lines is unknown. Method: Knockdown of GRP78 by siRNAs was performed to investigate the effect of GRP78 reduction in endoplasmic reticulum (ER)-stress induced and general apoptosis. Western blots examining apoptotic markers were performed on three HPV-negative HNSCC cell lines. WST-1 assay was performed to determine cell viability. In reverse, we utilized AA147, an ER proteostasis regulator to upregulate GRP78, and apoptotic markers and cell viability were determined. To test the ability of YUM70 to reverse cisplatin resistance, cisplatin-resistant HNSCC cell lines were generated by prolonged, repeated exposure to increasing concentrations of cisplatin. Colony formation assay using the cisplatin-resistant HNSCC cell line was performed to assess the Results: Reduction of GRP78 level induced HNSCC cell death while GRP78 upregulation conferred higher resistance to cisplatin. Combined cisplatin and YUM70 treatment increased apoptotic markers in the cisplatin-resistant HNSCC cell line, associating with reduced cell viability and clonogenicity. The combination treatment also increased apoptotic markers in the 3D spheroid model. Conclusion: The GRP78 inhibitor YUM70 reduced HNSCC cell viability and re-sensitized cisplatin-resistant HNSCC cell line in both 2D and 3D spheroid models, suggesting the potential use of YUM70 in the treatment of HNSCC, including cisplatin-resistant HNSCC.
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