ArticlePloS one2013
Endoplasmic reticulum stress signaling is involved in mitomycin C (MMC)-induced apoptosis in human fibroblasts via PERK pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 51 citations in OpenAlex.
- Acacetin reduces endoplasmic reticulum stress through the P-eNOS/PERK signaling pathway to attenuate MGO-induced vascular endothelial cell dysfunction.FEBS open bio · 2025Article
- Tumoricidal Efficacy of Artesunate-Eluting Microsphere: Differential Role of Bax/Bak in Orchestration of Cell Death Pathways.Biomaterials research · 2025Article
- Article
- Regulation of cardiac fibroblast cell death by unfolded protein response signaling.Frontiers in physiology · 2023Review
- The Role of Bioactive Compounds in Natural Products Extracted from Plants in Cancer Treatment and Their Mechanisms Related to Anticancer Effects.Oxidative medicine and cellular longevity · 2022Review
- Targeting the integrated stress response in ophthalmology.Current eye research · 2021Review
- Signalling and putative therapeutic molecules on the regulation of synoviocyte signalling in rheumatoid arthritis.Bone & joint research · 2021Article
- New insights into the activation of Radiation Desiccation Response regulon inJournal of biosciences · 2021Article
- The clinical significance and function of miR-146 in the promotion of epidural fibrosis.Genetics and molecular biology · 2021Article
- Unraveling the regulatory role of endoplasmic-reticulum-associated degradation in tumor immunity.Critical reviews in biochemistry and molecular biology · 2020Review
- Titanium dioxide nanoparticles induce endoplasmic reticulum stress-mediated apoptotic cell death in liver cancer cells.The Journal of international medical research · 2020Article
- The dietary triterpenoid 18α-Glycyrrhetinic acid protects from MMC-induced genotoxicity through the ERK/Nrf2 pathway.Redox biology · 2020Article
- Artesunate prevents knee intraarticular adhesion via PRKR-like ER kinase (PERK) signal pathway.Journal of orthopaedic surgery and research · 2019Article
- Pirfenidone inhibits epidural scar fibroblast proliferation and differentiation by regulating TGF-β1-induced Smad-dependent and -independent pathways.American journal of translational research · 2019Article
- Anticancer therapy and lung injury: molecular mechanisms.Expert review of anticancer therapy · 2018Review
- Targeting Oxidatively Induced DNA Damage Response in Cancer: Opportunities for Novel Cancer Therapies.Oxidative medicine and cellular longevity · 2018Review
- Mitomycin C induces apoptosis in human epidural scar fibroblasts after surgical decompression for spinal cord injury.Neural regeneration research · 2017Article
- Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Oxidative medicine and cellular longevity · 2017Article
- Glycyrrhetinic acid induces G1‑phase cell cycle arrest in human non‑small cell lung cancer cells through endoplasmic reticulum stress pathway.International journal of oncology · 2015Article
- Up-regulation of endoplasmic reticulum stress induced genes of the unfolded protein response in the liver of periparturient dairy cows.BMC veterinary research · 2014Article
Corrections and comments
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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
Endoplasmic reticulum (ER) stress-mediated cell apoptosis has been implicated in various cell types, including fibroblasts. Previous studies have shown that mitomycin C (MMC)-induced apoptosis occurs in fibroblasts, but the effects of MMC on ER stress-mediated apoptosis in fibroblasts have not been examined. Here, MMC-induced apoptosis in human primary fibroblasts was investigated by exposing cells to a single dose of MMC for 5 minutes. Significant inhibition of cell proliferation and increased apoptosis were observed using a cell viability assay, Annexin V/propidium iodide double staining, cell cycle analysis, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. Upregulation of proapoptotic factors, including cleaved caspase-3 and poly ADP-ribose polymerase (PARP), was detected by Western blotting. MMC-induced apoptosis was correlated with elevation of 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP), which are hallmarks of ER stress. Three unfolded protein response (UPR) sensors (inositol-requiring enzyme 1, IRE1; activating transcription factor 6, ATF6; and PKR-like ER kinase, PERK) and their downstream signaling pathways were also activated. Knockdown of CHOP attenuated MMC-induced apoptosis by increasing the ratio of BCL-2/BAX and decreasing BIM expression, suggesting that ER stress is involved in MMC-induced fibroblast apoptosis. Interestingly, knockdown of PERK significantly decreased ER stress-mediated apoptosis by reducing the expression of CHOP, BIM and cleaved caspase-3. Reactive oxygen species (ROS) scavenging also decreased the expression of GRP78, phospho-PERK, CHOP, and BIM. These results demonstrate that MMC-induced apoptosis is triggered by ROS generation and PERK activation.
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