ArticlePloS one2013
Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells.
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 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Meta-Analysis of Oxaliplatin-Based Chemotherapy Combined With Traditional Medicines for Colorectal Cancer: Contributions of Specific Plants to Tumor Response.Integrative cancer therapies · 2016Pooled it
- Exploring natural products as apoptosis modulators in cancers: insights into natural product-based therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting endoplasmic reticulum stress-induced CLGN resensitizes hepatocellular carcinoma to apoptosis: paeonol synergistically enhances efficacy by dual inhibition of CLGN and NF-κB.Frontiers in oncology · 2025Article
- Resistance to the platinum‑based chemotherapeutic drugs in oral cancer: Focus on the role of p22phox (Review).Biomedical reports · 2024Review
- Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy.Frontiers in pharmacology · 2023Review
- Paeonol induces antitumor effects in hepatocellular carcinoma cells through survivin via the cyclooxygenase-2/prostaglandin E2 signaling pathway.Translational cancer research · 2020Article
- Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment.International journal of molecular sciences · 2020Review
- Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition.Cancer management and research · 2020Article
- Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-Mediators of inflammation · 2020Article
- Endoplasmic Reticulum Stress-Induced Resistance to Doxorubicin Is Reversed by Mulberry Leaf Polyphenol Extract in Hepatocellular Carcinoma through Inhibition of COX-2.Antioxidants (Basel, Switzerland) · 2019Article
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- The Role of the ER-Induced UPR Pathway and the Efficacy of Its Inhibitors and Inducers in the Inhibition of Tumor Progression.Oxidative medicine and cellular longevity · 2019Review
- Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review.Nutrients · 2018Review
- Paeonol exerts potential activities to inhibit the growth, migration and invasion of human gastric cancer BGC823 cells via downregulating MMP‑2 and MMP‑9.Molecular medicine reports · 2017Article
- Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2017Article
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- Synergistic anti-tumor efficacy of doxorubicin and flavopiridol in an in vivo hepatocellular carcinoma model.Journal of cancer research and clinical oncology · 2015Article
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Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndoplasmic reticulum stress (ER stress) is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone), is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress-induced resistance to chemotherapeutic agents in hepatocellular carcinoma (HCC) are poorly understood. METHODOLOGY/PRINCIPAL
findingsIn this study, we investigated the effect of the endoplasmic reticulum (ER) stress response during resistance of human hepatocellular carcinoma cells to doxorubicin. Treatment with the ER stress-inducer tunicamycin (TM) before the addition of doxorubicin reduced the rate of apoptosis induced by doxorubicin. Interestingly, co-pretreatment with tunicamycin and Pae significantly increased apoptosis induced by doxorubicin. Furthermore, induction of ER stress resulted in increasing expression of COX-2 concomitant with inactivation of Akt and up-regulation of the pro-apoptotic transcription factor CHOP (GADD153) in HepG2 cells. These cellular changes in gene expression and Akt activation may be an important resistance mechanism against doxorubicin in hepatocellular carcinoma cells undergoing ER stress. However, co-pretreatment with tunicamycin and Pae decreased the expression of COX-2 and levels of activation of Akt as well as increasing the levels of CHOP in HCC cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Pae reverses ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by targeting COX-2 mediated inactivation of PI3K/AKT/CHOP.
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