ArticleScientific reports2021
Cytoplasmic vacuolation with endoplasmic reticulum stress directs sorafenib induced non-apoptotic cell death in hepatic stellate cells.
Article in Scientific reports, 2021. 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, 28 citations in OpenAlex.
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- GPR143 mediates virus-induced cytoplasmic vacuolation through the MKK6-p38 pathway in teleosts.Zoological research · 2026Article
- High-Intensity Interval Training Attenuates Hepatic Fibrosis by Remodeling Lactate Metabolism in MASLD.Metabolites · 2026Article
- Binding and transport functions of human serum albumin and its clinical implications in liver disease: a narrative review.Translational gastroenterology and hepatology · 2026Review
- Gilteritinib suppresses prostate cancer cell proliferation and migration and induces ER stress-mediated non-autophagic cytoplasmic vacuolization cell death.Medical oncology (Northwood, London, England) · 2025Article
- Cytoplasmic Vacuolization: A Fascinating Morphological Alteration From Cellular Stress to Cell Death.Cancer science · 2025Review
- Glucosamine Inhibits the Proliferation of Hepatocellular Carcinoma Cells by Eliciting Apoptosis, Autophagy, and the Anti-Warburg Effect.Scientifica · 2025Article
- Survivin inhibition ameliorates liver fibrosis by inducing hepatic stellate cell senescence and depleting hepatic macrophage population.Journal of cell communication and signaling · 2024Article
- Kinetic Effects of Transferrin-Conjugated Gold Nanoparticles on the Antioxidant Glutathione-Thioredoxin Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Surface Immobilization of Anti-VEGF Peptide on SPIONs for Antiangiogenic and Targeted Delivery of Paclitaxel in Non-Small-Cell Lung Carcinoma.ACS applied bio materials · 2023Article
- Primary assessment of medicines for expected migrastatic potential with holographic incoherent quantitative phase imaging.Biomedical optics express · 2023Article
- Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Nigella sativa seeds mitigate the hepatic histo-architectural and ultrastructural changes induced by 4-nonylphenol in Clarias gariepinus.Scientific reports · 2023Article
- Divergent effect of Birinapant, and BV6 SMAC mimetic on TNFα induced NF-κB signaling and cell viability in activated hepatic stellate cells.Molecular biology reports · 2023Article
- Transcriptomic profiling on localized gastric cancer identified CPLX1 as a gene promoting malignant phenotype of gastric cancer and a predictor of recurrence after surgery and subsequent chemotherapy.Journal of gastroenterology · 2022Article
- Differences in the characteristics and pulmonary toxicity of nano- and micron-sized respirable coal dust.Respiratory research · 2022Article
- Antioxidant Effects of Irisin in Liver Diseases: Mechanistic Insights.Oxidative medicine and cellular longevity · 2022Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activated hepatic stellate cells (HSCs) are the major cells that secrete the ECM proteins and drive the pathogenesis of fibrosis in chronic liver disease. Targeting of HSCs by modulating their activation and proliferation has emerged as a promising approach in the development of anti-fibrotic therapy. Sorafenib, a multi-kinase inhibitor has shown anti-fibrotic properties by inhibiting the survival and proliferation of HSCs. In present study we investigated sorafenib induced cytoplasmic vacuolation mediated decreased cell viability of HSCs in dose and time dependent manner. In this circumstance, sorafenib induces ROS and ER stress in HSCs without involvement of autophagic signals. The protein synthesis inhibitor cycloheximide treatment significantly decreased the sorafenib-induced cytoplasmic vacuolation with increasing cell viability. Antioxidant human serum albumin influences the viability of HSCs by reducing sorafenib induced vacuolation and cell death. However, neither caspase inhibitor Z-VAD-FMK nor autophagy inhibitor chloroquine could rescue the HSCs from sorafenib-induced cytoplasmic vacuolation and cell death. Using TEM and ER organelle tracker, we conclude that the cytoplasmic vacuoles are due to ER dilation. Sorafenib treatment induces calreticulin and GPR78, and activates IRE1α-XBP1s axis of UPR pathway, which eventually trigger the non-apoptotic cell death in HSCs. This study provides a notable mechanistic insight into the ER stress directed non-apoptotic cell death with future directions for the development of efficient anti-fibrotic therapeutic strategies.
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