ArticleCancers2019
Inhibition of protein phosphatase 1 stimulates noncanonical ER stress eIF2α activation to enhance fisetin-induced chemosensitivity in HDAC inhibitor-resistant hepatocellular carcinoma cells.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Disrupting CARMA3 Signaling with Triptolide Reverses Sorafenib Resistance in Hepatocellular Carcinoma.International journal of medical sciences · 2025Article
- Fisetin reduces the resistance of MOLT-4 and K562 cells to TRAIL-induced apoptosis through upregulation of TRAIL receptors.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR-342-5p/CFL1.Cancer cell international · 2024Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Article
- Daidzein Synergizes with Gefitinib to Induce ROS/JNK/c-Jun Activation and Inhibit EGFR-STAT/AKT/ERK Pathways to enhance Lung Adenocarcinoma cells chemosensitivity.International journal of biological sciences · 2022Article
- Article
- Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines.Molecules (Basel, Switzerland) · 2021Article
- Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles.The EPMA journal · 2021Review
- RFX1: a promising therapeutic arsenal against cancer.Cancer cell international · 2021Review
- Hsa-miR-107 regulates chemosensitivity and inhibits tumor growth in hepatocellular carcinoma cells.Aging · 2021Article
- Article
- Fabrication of Supercritical Antisolvent (SAS) Process-Assisted Fisetin-Encapsulated Poly (Vinyl Pyrrolidone) (PVP) Nanocomposites for Improved Anticancer Therapy.Nanomaterials (Basel, Switzerland) · 2020Article
- CCT020312 Inhibits Triple-Negative Breast Cancer Through PERK Pathway-Mediated G1 Phase Cell Cycle Arrest and Apoptosis.Frontiers in pharmacology · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 8 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is a common fatal type of malignant tumor that has highly metastatic and recurrent properties. Fisetin is a natural flavonoid found in various vegetables and fruits which exhibits anti-cancer and anti-inflammatory properties, as well as other effects. Thus, we hypothesized that fisetin can act as an adjuvant therapy in cancer or drug-resistant cancer cells, and further investigated the molecular mechanisms underlying the development of drug-resistance in HCC cells. We found that fisetin effectively inhibited the cell viability of not only parental cells but also histone deacetylase inhibitors-resistant (HDACis-R) cells and enhanced the chemosensitivity of HCC cells. Interestingly, fisetin did not induce cell apoptosis through the activation of the endoplasmic reticulum (ER) stress sensor of protein kinase R (PKR)-like endoplasmic reticulum kinase, but rather through the non-canonical pathway of the protein phosphatase 1 (PP1)-mediated suppression of eIF2α phosphorylation. Moreover, fisetin-induced cell apoptosis was reversed by treatment with PP1 activator or eIF2α siRNA in HCC cells. Based on these observations, we suggest that PP1-eIF2α pathways are significantly involved in the effect of fisetin on HCC apoptosis. Thus, fisetin may act as a novel anticancer drug and new chemotherapy adjuvant which can improve the efficacy of chemotherapeutic agents and diminish their side-effects.
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Registered trials
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.