ArticleMedical oncology (Northwood, London, England)2015
Hesperetin induces the apoptosis of hepatocellular carcinoma cells via mitochondrial pathway mediated by the increased intracellular reactive oxygen species, ATP and calcium.
Article in Medical oncology (Northwood, London, England), 2015. 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 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 77 citations in OpenAlex.
- Therapeutic potential and molecular mechanisms of citrus flavonoids in hepatocellular carcinoma.Frontiers in pharmacology · 2026Review
- Article
- Preparation of mitochondria-targeted gold nanoprobes and their SERS application in the detection of DON-induced apoptosis.Analytical and bioanalytical chemistry · 2025Article
- Click on Click: Click-Flavone Glycosides Encapsulated in Click-Functionalised Polymersomes for Glioblastoma Therapy.Pharmaceutics · 2025Article
- Updated Review on Natural Polyphenols: Molecular Mechanisms, Biological Effects, and Clinical Applications for Cancer Management.Biomolecules · 2025Review
- The inhibitory effects ofIn silico pharmacology · 2025Article
- Review
- Flavonoids: Antioxidant Powerhouses and Their Role in Nanomedicine.Antioxidants (Basel, Switzerland) · 2024Review
- Gut microbiota mediates the pro-pyroptosis effect of xierezhuyubuxu decoction in hepatocellular carcinoma.Frontiers in microbiology · 2024Article
- Novel Strategies for Tumor Treatment: Harnessing ROS-Inducing Active Ingredients from Traditional Chinese Medicine Through Multifunctional Nanoformulations.International journal of nanomedicine · 2024Review
- Phytobioactive compounds as therapeutic agents for human diseases: A review.Food science & nutrition · 2023Review
- Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Hesperidin Suppresses the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress and Disrupting CaAntioxidants (Basel, Switzerland) · 2022Article
- Identification of the critical genes and miRNAs in hepatocellular carcinoma by integrated bioinformatics analysis.Medical oncology (Northwood, London, England) · 2022Article
- Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review.Heliyon · 2022Review
- Hesperidin Inhibits the p53-MDMXInteraction-Induced Apoptosis of Non-Small-Cell Lung Cancer and Enhances the Antitumor Effect of Carboplatin.Journal of oncology · 2022Article
- Hesperidin Reduces Memory Impairment Associated with Adult Rat Hippocampal Neurogenesis Triggered by Valproic Acid.Nutrients · 2021Article
- Anti-Hepatocellular Carcinoma Biomolecules: Molecular Targets Insights.International journal of molecular sciences · 2021Review
- Hesperetin attenuates silica-induced lung injury by reducing oxidative damage and inflammatory response.Experimental and therapeutic medicine · 2021Article
- Anticancer activity of flavonoids accompanied by redox state modulation and the potential for a chemotherapeutic strategy.Food science and biotechnology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hesperetin, a flavonoid from citrus fruits, has been proved to possess biological activity on various types of human cancers. However, few related studies on hepatocellular carcinoma are available. In this study, we aimed to investigate the effect of hesperetin on hepatocellular carcinoma cells in vitro and in vivo and clarify its potentially specific mechanism. Compared with the control group, the proliferations of hepatocellular carcinoma cells in hesperetin groups were significantly inhibited (P < 0.05), and a dose- and time-dependent inhibition of cell viability was observed. When pretreated with H2O2 (1 mM) or N-acetyl-L-cysteine (5 mM), the inhibition of cell viability by hesperetin was enhanced or reduced, respectively (P < 0.05). Similarly, the levels of intracellular ROS, ATP and Ca(2+) changed in different groups (P < 0.05). The results of Hoechst 33258 staining showed that the percentages of apoptotic cells in hesperetin groups are remarkably higher than that in control group (P < 0.05). And the results of Western blot showed that hesperetin caused an increase in the levels of cytosolic AIF, cytosolic Apaf-1, cytosolic Cyt C, caspase-3, caspase-9 and Bax and a decrease in that of Bcl-2, mitochondrial AIF, mitochondrial Apaf-1 and mitochondrial Cyt C (P < 0.05). Meanwhile, hesperetin significantly inhibited the growth of xenograft tumors. Our study suggests that hesperetin could inhibit the proliferation and induce the apoptosis of hepatocellular carcinoma via triggering the activation of the mitochondrial pathway by increasing the levels of intracellular ROS, ATP and Ca(2+).
Indexed as
Identifiers
What OpenQuestion holds
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.