ArticleActa pharmacologica Sinica2019
Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway.
Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- Incredible use of plant-derived bioactives as anticancer agents.RSC advances · 2025Review
- Chemical profiling and cytotoxic potential of the n-butanol fraction of Tamarix nilotica flowers.BMC complementary medicine and therapies · 2023Article
- Protective Effects of Astilbin Against Cadmium-Induced Apoptosis in Chicken Kidneys via Endoplasmic Reticulum Stress Signaling Pathway.Biological trace element research · 2022Article
- Molecular Targets and Mechanisms ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Interaction between COX-2 and ER stress is involved in the apoptosis-induced myocardial ischemia/reperfusion injury.American journal of translational research · 2022Article
- Anti-growth and pro-apoptotic effects of dasatinib on human oral cancer cells through multi-targeted mechanisms.Journal of cellular and molecular medicine · 2021Article
- Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells.Biomolecules · 2021Article
- Gambogic Acid Inhibits Wnt/β-catenin Signaling and Induces ER Stress-Mediated Apoptosis in Human Cholangiocarcinoma.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- The Effect of Hispidulin, a Flavonoid fromMolecules (Basel, Switzerland) · 2021Article
- Retraction Note to: Chrysophanol exhibits anti-cancer activities in lung cancer cell through regulating ROS/HIF-1a/VEGF signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Hispidulin modulates epithelial-mesenchymal transition in breast cancer cells.Oncology letters · 2021Article
- Identification and Quantification of Phenolic Compounds from Mexican Oregano (Molecules (Basel, Switzerland) · 2021Article
- 6-Methoxylated Flavonoids: Jacein, and 3-demethyljacein fromIranian journal of pharmaceutical research : IJPR · 2021Article
- Protective action of the ginsenoside Rh3 in a rat myocardial ischemia-reperfusion injury model by inhibition of apoptosis induced via p38 mitogen-activated protein kinase/caspase-3 signaling.The Journal of international medical research · 2020Article
- Hispidulin exhibits potent anticancer activity in vitro and in vivo through activating ER stress in non‑small‑cell lung cancer cells.Oncology reports · 2020Article
- Natural Products Targeting ER Stress, and the Functional Link to Mitochondria.International journal of molecular sciences · 2020Review
- Chrysophanol suppresses growth and metastasis of T cell acute lymphoblastic leukemia via miR-9/PD-L1 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- β-elemene enhances cisplatin-induced apoptosis in bladder cancer cells through the ROS-AMPK signaling pathway.Oncology letters · 2020Article
- Benzophenones fromMolecules (Basel, Switzerland) · 2019Article
- Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
- Retraction · 2021-09-07Duplication of/in Image · Paper Mill · Unreliable Data · · see : https://docs.google.com/spreadsheets/d/13K6zoo2oSATsFlY7YGyvm2_Xs1jibs0RH4nKQP5y8DY/edit?usp=sharing
- Retracted
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hispidulin (4',5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid isolated from the medicinal plant S. involucrata, which exhibits anti-neoplastic activity against several types of cancer. However, the mechanism underlying its anti-cancer activity against hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, we investigated whether and how hispidulin-induced apoptosis of human HCC cells in vitro and in vivo. We showed that hispidulin (10, 20 μmol/L) dose-dependently inhibited cell growth and promoted apoptosis through mitochondrial apoptosis pathway in human HCC SMMC7721 cells and Huh7 cells. More importantly, we revealed that its pro-apoptotic effects depended on endoplasmic reticulum stress (ERS) and unfolded protein response (UPR), as pretreatment with salubrinal, a selective ERS inhibitor, or shRNA targeting a UPR protein CHOP effectively abrogated hispidulin-induced cell apoptosis. Furthermore, we showed that hispidulin-induced apoptosis was mediated by activation of AMPK/mTOR signaling pathway as pretreatment with Compound C, an AMPK inhibitor, or AMPK-targeting siRNA reversed the pro-apoptotic effect of hispidulin. In HCC xenograft nude mice, administration of hispidulin (25, 50 mg/kg every day, ip, for 27 days) dose-dependently suppressed the tumor growth, accompanied by inducing ERS and apoptosis in tumor tissue. Taken together, our results demonstrate that hispidulin induces ERS-mediated apoptosis in HCC cells via activating the AMPK/mTOR pathway. This study provides new insights into the anti-tumor activity of hispidulin in HCC.
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