ArticleOxidative medicine and cellular longevity2019
Hsp90 Inhibitor SNX-2112 Enhances TRAIL-Induced Apoptosis of Human Cervical Cancer Cells via the ROS-Mediated JNK-p53-Autophagy-DR5 Pathway.
Article in Oxidative medicine and cellular longevity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 38 citations in OpenAlex.
- PAX9 activates autophagy through a transcription-dependent mechanism, promoting EGFR degradation to restrict cell survival in oral cancer.British journal of cancer · 2026Article
- Comprehensive Analyses of PANoptosome with Potential Implications in Cancer Prognosis and Immunotherapy.Biochemical genetics · 2025Article
- Advances in the study of death receptor 5.Frontiers in pharmacology · 2025Review
- Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy.Frontiers in oncology · 2025Article
- RIOK3 sustains colorectal cancer cell survival under glucose deprivation via an HSP90α-dependent pathway.Oncogenesis · 2024Article
- The potential role of HPV oncoproteins in the PD-L1/PD-1 pathway in cervical cancer: new perspectives on cervical cancer immunotherapy.Frontiers in oncology · 2024Review
- c-Jun N-terminal kinase signaling in cellular senescence.Archives of toxicology · 2023Review
- Transcriptional regulation of autophagy and its implications in human disease.Cell death and differentiation · 2023Review
- PAK4-relevant proliferation reduced by cell autophagy via p53/mTOR/p-AKT signaling.Translational cancer research · 2023Article
- Organelle-targeted therapies: a comprehensive review on system design for enabling precision oncology.Signal transduction and targeted therapy · 2022Review
- p53 Modulation of Autophagy Signaling in Cancer Therapies: Perspectives Mechanism and Therapeutic Targets.Frontiers in cell and developmental biology · 2022Review
- Mechanism of HSP90 Inhibitor in the Treatment of DSS-induced Colitis in Mice by Inhibiting MAPK Pathway and Synergistic Effect of Compound Sophorae Decoction.Current pharmaceutical design · 2022Article
- Hsp90 up-regulates PD-L1 to promote HPV-positive cervical cancer via HER2/PI3K/AKT pathway.Molecular medicine (Cambridge, Mass.) · 2021Article
- Discovery of an orally active antitumor agent that induces apoptosis and suppresses EMT through heat shock protein 90 inhibition.Investigational new drugs · 2021Article
- Identification of a tumor microenvironment-related seven-gene signature for predicting prognosis in bladder cancer.BMC cancer · 2021Article
- Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.Frontiers in immunology · 2021Review
- An Overview of Novel Agents for Cervical Cancer Treatment by Inducing Apoptosis: Emerging Drugs Ongoing Clinical Trials and Preclinical Studies.Frontiers in medicine · 2021Review
- CASK Silence Overcomes Sorafenib Resistance of Hepatocellular Carcinoma Through Activating Apoptosis and Autophagic Cell Death.Frontiers in oncology · 2021Article
- Complex Crystal Structure Determination andFrontiers in cell and developmental biology · 2021Article
- Ferroptosis Activation Scoring Model Assists in Chemotherapeutic Agents' Selection and Mediates Cross-Talk With Immunocytes in Malignant Glioblastoma.Frontiers in immunology · 2021Article
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12 authors at 1 institution in 1 country.
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Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell apoptosis-inducing factor that can induce apoptosis in a variety of cancer cells. However, resistance to TRAIL in cancer cells is a huge obstacle in creating effective TRAIL-targeted clinical therapies. Thus, agents that can either enhance the effect of TRAIL or overcome its resistance are needed. In this study, we combined TRAIL with SNX-2112, an Hsp90 inhibitor we previously developed, to explore the effect and mechanism that SNX-2112 enhanced TRAIL-induced apoptosis in cervical cancer cells. Our results showed that SNX-2112 markedly enhanced TRAIL-induced cytotoxicity in HeLa cells, and this combination was found to be synergistic. Additionally, we found that SNX-2112 sensitized TRAIL-mediated apoptosis caspase-dependently in TRAIL-resistant HeLa cells. Mechanismly, SNX-2112 downregulated antiapoptosis proteins, including Bcl-2, Bcl-XL, and FLIP, promoted the accumulation of reactive oxygen species (ROS), and increased the expression levels of p-JNK and p53. ROS scavenger NAC rescued SNX-2112/TRAIL-induced apoptosis and suppressed SNX-2112-induced p-JNK and p53. Moreover, SNX-2112 induced the upregulation of death-receptor DR5 in HeLa cells. The silencing of DR5 by siRNA significantly decreased cell apoptosis by the combined effect of SNX-2112 and TRAIL. In addition, SNX-2112 inhibited the Akt/mTOR signaling pathway and induced autophagy in HeLa cells. The blockage of autophagy by bafilomycin A1 or Atg7 siRNA abolished SNX-2112-induced upregulation of DR5. Meanwhile, ROS scavenger NAC, JNK inhibitor SP600125, and p53 inhibitor PFT
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