ArticleInternational journal of molecular sciences2017
Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells.
Article in International journal of molecular sciences, 2017. 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, 39 citations in OpenAlex.
- The molecular sub-type and the development and validation of a prognosis prediction model based on endocytosis-related genes for hepatocellular carcinoma.Journal of gastrointestinal oncology · 2025Article
- Repurposing Antiepileptic Drugs for Cancer: A Promising Therapeutic Strategy.Journal of clinical medicine · 2025Review
- Mechanism and application of HDAC inhibitors in the treatment of hepatocellular carcinoma.Journal of molecular medicine (Berlin, Germany) · 2025Review
- The contrasting regulatory effects of valproic acid on ferroptosis and disulfidptosis in hepatocellular carcinoma.Theranostics · 2025Article
- Unlocking Nature's Potential: Ferritin as a Universal Nanocarrier for Amplified Cancer Therapy Testing via 3D Microtissues.ACS applied materials & interfaces · 2024Article
- Article
- Identification and validation of a prognostic model of necroptosis-related lncRNAs in hepatocellular carcinoma.Frontiers in genetics · 2022Article
- Improved Anticancer Activities of a New Pentafluorothio-Substituted Vorinostat-Type Histone Deacetylase Inhibitor.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Reactive Oxygen Species-Mediated Mitochondrial Dysfunction Triggers Sodium Valproate-Induced Cytotoxicity in Human Colorectal Adenocarcinoma Cells.Journal of gastrointestinal cancer · 2021Article
- Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity against Leukemias and Lymphomas of Novel, Tricyclic Vorinostat Analogues.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Synergistic Growth Inhibition of HT-29 Colon and MCF-7 Breast Cancer Cells with Simultaneous and Sequential Combinations of Antineoplastics and CNS Drugs.International journal of molecular sciences · 2021Article
- Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities.Journal of personalized medicine · 2021Review
- GPR50 Promotes Hepatocellular Carcinoma Progression via the Notch Signaling Pathway through Direct Interaction with ADAM17.Molecular therapy oncolytics · 2020Article
- Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma.BioMed research international · 2020Review
- Epigenetic Control of Autophagy in Cancer Cells: A Key Process for Cancer-Related Phenotypes.Cells · 2019Review
- 2,4-Dihydroxy-3'-methoxy-4'-ethoxychalcone suppresses cell proliferation and induces apoptosis of multiple myelomaPharmaceutical biology · 2019Article
- Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells.BMC cancer · 2019Article
- Prospects for repurposing CNS drugs for cancer treatment.Oncology reviews · 2019Article
- The short-term effect of histone deacetylase inhibitors, chidamide and valproic acid, on the NF‑κB pathway in multiple myeloma cells.International journal of molecular medicine · 2019Article
- Combination chemotherapy of valproic acid (VPA) and gemcitabine regulates STAT3/Bmi1 pathway to differentially potentiate the motility of pancreatic cancer cells.Cell & bioscience · 2019Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.
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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 Socratic graph.