ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Hesperidin from Citrus seed induces human hepatocellular carcinoma HepG2 cell apoptosis via both mitochondrial and death receptor pathways.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Dietary Polyphenols-Important Non-Nutrients in the Prevention of Chronic Noncommunicable Diseases. A Systematic Review.Nutrients · 2019Pooled it
- Anticancer activity of Hebesu extracts in cancer cell lines.Anatomy & cell biology · 2026Article
- Agro-Industrial Plant Biomass as a Sustainable Source of Anticancer Polyphenols: Molecular Mechanisms and Future Perspectives.Current issues in molecular biology · 2026Review
- Therapeutic potential and molecular mechanisms of citrus flavonoids in hepatocellular carcinoma.Frontiers in pharmacology · 2026Review
- Hesperidin exacerbates the therapeutic potency of cisplatin against hepatocytotoxicity of Ehrlich ascites carcinoma in mice.Scientific reports · 2025Article
- Subcritical Water and Pressurised Ethanol Extractions for Maximum Recovery of Antioxidants from Orange Peel Herbal Dust with Evaluation of Its Pharmacological Potential Using In Silico and In Vitro Analysis.Antioxidants (Basel, Switzerland) · 2025Article
- The Dual Role of Dietary Phytochemicals in Oxidative Stress: Implications for Oncogenesis, Cancer Chemoprevention, and ncRNA Regulation.Antioxidants (Basel, Switzerland) · 2025Review
- Chitosan/Hesperidin Nanoparticles for Sufficient, Compatible, Antioxidant, and Antitumor Drug Delivery Systems.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Integrating molecular, biochemical, and immunohistochemical features as predictors of hepatocellular carcinoma drug response using machine-learning algorithms.Frontiers in molecular biosciences · 2024Article
- Article
- Anti-cancer effect of nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line.BMC complementary medicine and therapies · 2023Article
- Hesperidin, a Bioflavonoid in Cancer Therapy: A Review for a Mechanism of Action through the Modulation of Cell Signaling Pathways.Molecules (Basel, Switzerland) · 2023Review
- Phytobioactive compounds as therapeutic agents for human diseases: A review.Food science & nutrition · 2023Review
- Anti-cancer Effect and Active Phytochemicals of Houttuynia cordata Thunb. against Human Breast Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cells.Journal of the Egyptian National Cancer Institute · 2023Article
- Metabolomic Analysis of Phytochemical Compounds from Ethanolic Extract of Lime (Molecules (Basel, Switzerland) · 2023Article
- A Scientometric Study to a Critical Review on Promising Anticancer and Neuroprotective Compounds: Citrus Flavonoids.Antioxidants (Basel, Switzerland) · 2023Review
- Research progress on the anti-tumor effect of Naringin.Frontiers in pharmacology · 2023Review
- Role of Plant-Derived Active Constituents in Cancer Treatment and Their Mechanisms of Action.Cells · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Citrus seeds are full of phenolic compounds, such as flavonoids. The aims of this study were to identify the types of flavonoids in Citrus seed extracts, the cytotoxic effect, mode of cell death, and signaling pathway in human hepatic cancer HepG2 cells. The flavonoids contain anticancer, free radical scavenging, and antioxidant activities. Neohesperidin, hesperidin, and naringin, active flavanone glycosides, were identified in Citrus seed extract. The cytotoxic effect of three compounds was in a dose-dependent manner, and IC50 levels were determined. The sensitivity of human HepG2 cells was as follows: hesperidin > naringin > neohesperidin > naringenin. Hesperidin induced HepG2 cells to undergo apoptosis in a dose-dependent manner as evidenced by the externalization of phosphatidylserine and determined by annexin V-fluorescein isothiocyanate and propidium iodide staining using flow cytometry. Hesperidin did not induce the generation of reactive oxygen species, which was determined by using 2',7'-dichlorohydrofluorescein diacetate and flow cytometry method. The number of hesperidin-treated HepG2 cells with the loss of mitochondrial transmembrane potential increased concentration dependently, using 3,3'-dihexyloxacarbocyanine iodide employing flow cytometry. Caspase-9, -8, and -3 activities were activated and increased in hesperidin-treated HepG2 cells. Bcl-xL protein was downregulated whereas Bax, Bak, and tBid protein levels were upregulated after treatment with hesperidin in a dose-dependent manner. In conclusion, the bioflavanone from Citrus seeds, hesperidin, induced human HepG2 cell apoptosis via mitochondrial pathway and death receptor pathway. Citrus seed flavonoids are beneficial and can be developed as anticancer drug or food supplement, which still needs further in vivo investigation in animals and human beings.
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