ArticleCurrent issues in molecular biology2023
Hesperetin Induces Autophagy and Delayed Apoptosis by Modulating the AMPK/Akt/mTOR Pathway in Human Leukemia Cells In Vitro.
Article in Current issues in molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 18 citations in OpenAlex.
- Research Progress and Prospects of Flavonoids in the Treatment of Diseases by Regulating Autophagy: A Narrative Review.Molecules (Basel, Switzerland) · 2026Review
- Investigation of the Anticancer Effects and Senescence Induction of Hesperetin Combined with Cisplatin in Hepatocellular Carcinoma and Embryonic Fibroblast Cell Lines.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Spectrum and signals of medication-associated cognitive disorder: a comprehensive disproportionality analysis with cross-database validation.Frontiers in pharmacology · 2026Article
- Inhibition of PI3K/AKT/mTOR signaling enhances autophagy in HL-60 acute myeloid leukemia cells: An integrative bioinformatic and in vitro study.Biochemistry and biophysics reports · 2025Article
- Hesperetin Protects from Palmitic-Acid-Induced Lipotoxicity through the Inhibition of Glutaminolysis, mTORC1 Signaling, and Limited Apoptosis.Journal of agricultural and food chemistry · 2025Article
- Hesperetin increases membrane progesterone receptor expression in human myeloid leukemia cells and reduces ROS.Medical oncology (Northwood, London, England) · 2025Article
- Updated Review on Natural Polyphenols: Molecular Mechanisms, Biological Effects, and Clinical Applications for Cancer Management.Biomolecules · 2025Review
- Harnessing hesperidin for brain metabolism: epigenetic signatures, cellular homeostasis, synaptic function, and neuroprotection in age-related diseases and neurodegenerative diseases.Frontiers in nutrition · 2025Review
- Editorial for the Special Issue 'Molecular Mechanisms of Leukemia'.Current issues in molecular biology · 2024Article
- Hypomyelination Leukodystrophy 16 (HLD16)-Associated Mutation p.Asp252Asn of TMEM106B Blunts Cell Morphological Differentiation.Current issues in molecular biology · 2024Article
- Computational and Experimental Approaches Exploring the Role of Hesperetin in Improving Autophagy in Rat Diabetic Retinopathy.Biomedicines · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHesperetin has been reported to have anticancer properties. However, the molecular mechanisms underlying its action on leukemia cells remain unclear. This in vitro study evaluated the possible mechanisms of hesperetin in leukemia cells (HL-60 and U937).
methodsCell viability was evaluated using a cell counting kit-8 (CCK-8) assay. Apoptosis and autophagy assays were conducted through annexin V/PI staining and acidic vesicular organelle (AVO) staining. Cell cycle analysis was conducted through propidium iodide (PI) and flow cytometry. The expression of proteins related to apoptosis and autophagy, including cleaved-PARP-1, Bcl-2, Bax, LC3-I/II, Beclin-1, Atg5, p62, phospho-AMPK, AMPK, phospho-mTOR, mTOR, phospho-Akt, and Akt, in human leukemia cells were evaluated using Western blotting.
resultsHesperetin dose-dependently inhibited leukemia cell viability. However, we found a low degree of apoptosis and cell cycle arrest induced by hesperetin in U937 cells. These findings imply the presence of additional mechanisms modulating hesperetin-induced cell death. Next, we evaluated autophagy, the possible mechanism modulating cell death or survival, to clarify the underlying mechanism of hesperetin-induced cell death. Hesperetin also dose-dependently increased the ratio of LC3II/I, Atg5, and Beclin 1 and decreased p62. Moreover, 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) inhibited hesperetin-induced autophagy. We suggest that hesperetin can protect cancer cells during the transient period and may extend survival. Furthermore, a decrease in p-mTOR and p-Akt expression and an increase in p-AMPK expression were observed. Collectively, these findings suggest that hesperetin induces autophagy by modulating the AMPK/Akt/mTOR pathway.
conclusionHesperetin promoted cell death in the human leukemic cell line U937 by inducing a low degree of slight apoptosis, cell cycle arrest, and autophagy. It is therefore a potential adjuvant to antileukemia therapy and may be combined with other chemotherapeutic drugs to reduce chemoresistance and side effects.
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