ArticlePloS one2014
Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Targeting intracellular autophagic process for the treatment of post-stroke ischemia/reperfusion injury.Animal models and experimental medicine · 2025Review
- Curcumin and its Derivatives Targeting Multiple Signaling Pathways to Elicit Anticancer Activity: A Comprehensive Perspective.Current medicinal chemistry · 2024Review
- The Effect of Natural Substances Contained in Bee Products on Prostate Cancer in In Vitro Studies.Molecules (Basel, Switzerland) · 2023Article
- Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer.International journal of molecular sciences · 2023Review
- Review
- In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling.Cancers · 2021Review
- Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.International journal of molecular sciences · 2021Review
- Endoplasmic Reticulum Stress and Autophagy in the Pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Evidence and Perspectives.Current obesity reports · 2021Review
- Effect of autophagy on oxalate-induced toxicity of human proximal renal tubular epithelial cell.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Potential Role of Curcumin and Its Nanoformulations to Treat Various Types of Cancers.Biomolecules · 2021Review
- Curcumin Encapsulated in Crosslinked Cyclodextrin Nanoparticles Enables Immediate Inhibition of Cell Growth and Efficient Killing of Cancer Cells.Nanomaterials (Basel, Switzerland) · 2021Article
- Article
- Review
- Galangin Improved Non-Alcoholic Fatty Liver Disease in Mice by Promoting Autophagy.Drug design, development and therapy · 2020Article
- Bioactivity Evaluation of a Novel Formulated Curcumin.Nutrients · 2019Article
- Improved Survival in Hepatocellular Carcinoma Patients with Cardiac Arrhythmia by Amiodarone Treatment through Autophagy.International journal of molecular sciences · 2019Article
- Curcumin diethyl disuccinate, a prodrug of curcumin, enhances anti-proliferative effect of curcumin against HepG2 cells via apoptosis induction.Scientific reports · 2019Article
- Article
- Curcumin Induces Autophagy, Apoptosis, and Cell Cycle Arrest in Human Pancreatic Cancer Cells.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Fucoxanthin Activates Apoptosis via Inhibition of PI3K/Akt/mTOR Pathway and Suppresses Invasion and Migration by Restriction of p38-MMP-2/9 Pathway in Human Glioblastoma Cells.Neurochemical research · 2016Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Curcumin, a spice component as well as a traditional Asian medicine, has been reported to inhibit proliferation of a variety of cancer cells but is limited in application due to its low potency and bioavailability. Here, we have assessed the therapeutic effects of a novel and water soluble curcumin analog, 3,5-bis(2-hydroxybenzylidene)tetrahydro-4H-pyran-4-one glutathione conjugate [EF25-(GSH)2], on hepatoma cells. Using the MTT and colony formation assays, we determined that EF25-(GSH)2 drastically inhibits the proliferation of hepatoma cell line HepG2 with minimal cytotoxicity for the immortalized human hepatic cell line HL-7702. Significantly, EF25-(GSH)2 suppressed growth of HepG2 xenografts in mice with no observed toxicity to the animals. Mechanistic investigation revealed that EF25-(GSH)2 induces autophagy by means of a biphasic mechanism. Low concentrations (<5 µmol/L) induced autophagy with reversible and moderate cytoplasmic vacuolization, while high concentrations (>10 µmol/L) triggered an arrested autophagy process with irreversible and extensive cytoplasmic vacuolization. Prolonged treatment with EF25-(GSH)2 induced cell death through both an apoptosis-dependent and a non-apoptotic mechanism. Chloroquine, a late stage inhibitor of autophagy which promoted cytoplasmic vacuolization, led to significantly enhanced apoptosis and cytotoxicity when combined with EF25-(GSH)2. Taken together, these data imply a fail-safe mechanism regulated by autophagy in the action of EF25-(GSH)2, suggesting the therapeutic potential of the novel curcumin analog against hepatocellular carcinoma (HCC), while offering a novel and effective combination strategy with chloroquine for the treatment of patients with HCC.
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