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Methyl gallate, gallic acid-derived compound, inhibit cell proliferation through increasing ROS production and apoptosis in hepatocellular carcinoma cells
- Source :
- PLoS ONE, PLoS ONE, Vol 16, Iss 3, p e0248521 (2021)
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
Abstract
- Hepatocellular carcinoma (HCC) is a global health problem. Currently, there is no effective therapeutic strategy for HCC. Methyl gallate (MG), from plant-derived phenolic gallic acid, has exhibited antitumor efficacy. However, the effect of MG on HCC is unclear. In vitro growth activity was detected by a sulforhodamine assay. A zebrafish xenotransplantation was applied to evaluate the inhibitory effect of MG. Reactive oxygen species (ROS) production, autophagy, and lysosome formation were detected by specific dyes. Finally, apoptosis was examined using annexin V-FITC/PI staining and western blot was performed to determine the molecular mechanism. It was demonstrated that MG treatment inhibited the proliferation of Hep3B, Mahlavu, and HepJ5 cells. Xenotransplantation also showed that MG inhibited the growth of Hep3B and HepJ5 cells. MG treatment increased cellular levels of superoxide and oxidative stress. Increases in autophagy and lysosome formation were found after MG treatment. The western blot analysis showed that MG activated cleavage of caspase-3 and poly (SDP ribose) polymerase (PARP), modulated levels of the Bcl2, Bax, and Bad ligands, and induced apoptosis. MG induced autophagy with notable activation of beclin-1, autophagy related 5+12 (ATG5+12), and conversion of light chain 3-I (LC3-I) to II. Our study showed that MG exposure inhibited HCC proliferation both in vitro and in vivo. And blocking autophagy enhanced MG-induced cytotoxicity in HCC cells. These findings suggested MG might serve as a powerful therapeutic supplement for human HCC patients.
- Subjects :
- Cancer Treatment
Apoptosis
chemistry.chemical_compound
Superoxides
Antineoplastic Combined Chemotherapy Protocols
Medicine and Health Sciences
Cytotoxicity
Zebrafish
chemistry.chemical_classification
Multidisciplinary
Cell Death
Liver Diseases
Liver Neoplasms
Eukaryota
Oxides
Chloroquine
Animal Models
Chemistry
medicine.anatomical_structure
Oncology
Experimental Organism Systems
Cell Processes
Osteichthyes
Physical Sciences
Vertebrates
Medicine
Cellular Structures and Organelles
Research Article
Carcinoma, Hepatocellular
Science
Poly ADP ribose polymerase
Autophagic Cell Death
ATG5
Gastroenterology and Hepatology
Research and Analysis Methods
Model Organisms
Lysosome
Cell Line, Tumor
Gallic Acid
Gastrointestinal Tumors
medicine
Autophagy
Animals
Humans
Methyl gallate
Cell Proliferation
Reactive oxygen species
Carcinoma
Chemical Compounds
Organisms
Biology and Life Sciences
Cancers and Neoplasms
Cell Biology
Hepatocellular Carcinoma
Molecular biology
Xenograft Model Antitumor Assays
digestive system diseases
Oxidative Stress
Fish
chemistry
Animal Studies
Reactive Oxygen Species
Lysosomes
Zoology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 16
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....7b4aa4f122e900e68ad5e7fa1c27a430