ArticlePloS one2011
SB202190-induced cell type-specific vacuole formation and defective autophagy do not depend on p38 MAP kinase inhibition.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control.Cell death & disease · 2024Article
- SB202190 Predicts BRAF-Activating Mutations in Primary Colorectal Cancer Organoids via Erk1-2 Modulation.Cells · 2023Article
- Terpenoids' anti-cancer effects: focus on autophagy.Apoptosis : an international journal on programmed cell death · 2021Review
- Combined Inhibition of p38MAPK and PIKfyve Synergistically Disrupts Autophagy to Selectively Target Cancer Cells.Cancer research · 2021Article
- DCZ5248, a novel dual inhibitor of Hsp90 and autophagy, exerts antitumor activity against colon cancer.Acta pharmacologica Sinica · 2021Article
- Dual Targeting of BRAF and mTOR Signaling in Melanoma Cells with Pyridinyl Imidazole Compounds.Cancers · 2020Article
- A stress response p38 MAP kinase inhibitor SB202190 promoted TFEB/TFE3-dependent autophagy and lysosomal biogenesis independent of p38.Redox biology · 2020Article
- The sex-specific role of p38 MAP kinase in CNS autoimmunity is regulated by estrogen receptor alpha.Journal of neuroimmunology · 2020Article
- Autophagy-induced senescence is regulated by p38α signaling.Cell death & disease · 2019Article
- Article
- SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1.Oncotarget · 2018Article
- Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition.American journal of cancer research · 2018Article
- Anti-inflammatory roles of p38α MAPK in macrophages are context dependent and require IL-10.Journal of leukocyte biology · 2017Article
- Non-kinase targets of protein kinase inhibitors.Nature reviews. Drug discovery · 2017Review
- Clearance of Damaged Mitochondria Through PINK1 Stabilization by JNK and ERK MAPK Signaling in Chlorpyrifos-Treated Neuroblastoma Cells.Molecular neurobiology · 2017Article
- IL-1β-Induced Downregulation of the Multifunctional PDZ Adaptor PDZK1 Is Attenuated by ERK Inhibition, RXRα, or PPARα Stimulation in Enterocytes.Frontiers in physiology · 2017Article
- Role of p38Toxins · 2016Article
- Targeting neuronal MAPK14/p38α activity to modulate autophagy in the Alzheimer disease brain.Autophagy · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SB202190, a widely used inhibitor of p38 MAPKα and β, was recently described to induce autophagic vacuoles and cell death in colon and ovarian cancer cells lines and, therefore, this effect was supposed to be specific for transformed cells and to open therapeutic options. Here, we demonstrate that SB202190 and the structurally related inhibitor SB203580 induce pro-autophagic gene expression and vacuole formation in various cancer and non-cancer cell lines of human, rat, mouse and hamster origin. This effect seems to induce defective autophagy leading to the accumulation of acidic vacuoles, p62 protein and lipid conjugated LC3. Using further p38 inhibitors we show that p38 MAPK inhibition is not sufficient for the autophagic response. In line with these results, expression of a SB202190-resistant mutant of p38α, which significantly increases activity of the p38 pathway under inhibitory conditions, does not block SB202190-dependent vacuole formation, indicating that lack of p38α activity is not necessary for this effect. Obviously, the induction of autophagic vacuole formation by SB203580 and SB202190 is due to off-target effects of these inhibitors on post-translational protein modifications, such as phosphorylation of the MAPKs ERK1/2 and JNK1/2, ribosomal protein S6, and PKB/Akt. Interestingly, the PI3K-inhibitor wortmannin induces transient vacuole formation indicating that the PI3K-PKB/Akt-mTOR pathway is essential for preventing autophagy and that cross-inhibition of this pathway by SB202190 could be the reason for the early part of the effect observed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.