ArticleInternational journal of molecular sciences2017
Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 65 citations in OpenAlex.
- Fisetin alleviates pulmonary arterial hypertension by inhibiting the TGF-β1/Smad 2/3 signaling pathway.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Osthole attenuates trastuzumab-induced cardiotoxicity in mice by enhancing autophagy via regulating the p38MAPK/mTOR signaling pathway.Journal of traditional and complementary medicine · 2026Article
- Regulatory Dynamics of Nrf2 With Sirtuins in the Brain: Exploring Cellular Metabolism, Synaptic Plasticity, and Defense Mechanisms.Journal of neurochemistry · 2025Review
- Farnesol Improves Endoplasmic Reticulum Stress and Hepatic Metabolic Dysfunction Induced by Tunicamycin in Mice.Biology · 2025Article
- The protective effects of fisetin in metabolic disorders: a focus on oxidative stress and associated events.Journal of diabetes and metabolic disorders · 2024Review
- Cigarette Smoke Extract Induces MUC5AC Expression Through the ROS/ IP3R/CaInternational journal of chronic obstructive pulmonary disease · 2024Article
- Neuroprotective effects of flavonoids: endoplasmic reticulum as the target.Frontiers in neuroscience · 2024Review
- An Overview of Recent Advances in the Neuroprotective Potentials of Fisetin against Diverse Insults in Neurological Diseases and the Underlying Signaling Pathways.Biomedicines · 2023Review
- The Neuroprotective Effects of Flavonoid Fisetin against Corticosterone-Induced Cell Death through Modulation of ERK, p38, and PI3K/Akt/FOXO3a-Dependent Pathways in PC12 Cells.Pharmaceutics · 2023Article
- Fisetin Protects C2C12 Mouse Myoblasts from Oxidative Stress-Induced Cytotoxicity through Regulation of the Nrf2/HO-1 Signaling.Journal of microbiology and biotechnology · 2023Article
- Fisetin, an Anti-Inflammatory Agent, Overcomes Radioresistance by Activating the PERK-ATF4-CHOP Axis in Liver Cancer.International journal of molecular sciences · 2023Article
- Unfolding the Interactions between Endoplasmic Reticulum Stress and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress.International journal of molecular sciences · 2023Article
- Attenuation of N-Nitrosodiethylamine -Induced Hepatocellular Carcinoma by Piceatannol and/or Cisplatin: The Interplay between Nuclear Factor (Erythroid Derived 2)-like 2 and Redox Status.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Bisimidazolium Salt Glycosyltransferase Inhibitors Suppress Hepatocellular Carcinoma Progression In Vitro and In Vivo.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Fisetin Attenuates Doxorubicin-Induced CardiomyopathyFrontiers in pharmacology · 2021Article
- 5,6,7,4'-Tetramethoxyflavanone attenuates NADPH oxidase 1/4 and promotes sirtuin-1 to inhibit cell stress, senescence and apoptosis in Aß25-35-mediated SK-N-SH dysfunction.EXCLI journal · 2021Article
- Fisetin Prevents Acetaminophen-Induced Liver Injury by Promoting Autophagy.Frontiers in pharmacology · 2020Article
- SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases.Frontiers in pharmacology · 2020Review
- Nrf2⁻ARE Signaling Acts as Master Pathway for the Cellular Antioxidant Activity of Fisetin.Molecules (Basel, Switzerland) · 2019Article
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
backgroundFisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells.
methodsCell viability was assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptotic and autophagic markers were analyzed by Western blot. Gene expression of unfolded protein response (UPR) and Phase II enzymes was further investigated using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using 2',7'-dichlorodihydrofluorescein diacetate (H₂DCFDA) by a fluorometer. The effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1 (Sirtuin 1) signaling pathways were examined using Western blotting and specific inhibitors.
resultsFisetin (<20 µM) restored cell viability and repressed apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2-targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal-regulated kinase), JNK (c-JUN NH₂-terminal protein kinase), and p38 MAPK. Addition of JNK and p38 MAPK inhibitor significantly antagonized its cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm-inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor) significantly blocked fisetin-mediated cytoprotection. In conclusion, this result shows that fisetin activates Nrf2, MAPK and SIRT1, which may elicit adaptive cellular stress response pathways so as to protect cells from Tm-induced cytotoxicity.
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