ABSTRACT
Helicobacter pylori infection is associated with high incidence of gastric diseases. The extensive therapy of H. pylori infection with antibiotics has increased its resistance rates worldwide. Ovatodiolide, a pure constituent isolated from Anisomeles indica, has been demonstrated to possess bactericidal activity against H. pylori. In this study, ovatodiolide inhibited the growth of both H. pylori reference strain and clinical multidrug-resistant isolates. Docking analysis revealed that ovatodiolide fits into the hydrophobic pocket of a ribosomal protein, RpsB. Furthermore, ovatodiolide inhibited bacterial growth by reducing levels of RpsB, which plays a crucial role in protein translation. Our results demonstrate that ovatodiolide binds to a ribosomal protein and interferes with protein synthesis. This study provides evidence that ovatodiolide has the potential to be developed into a potent therapeutic agent for treating H. pylori infection.
Subject(s)
Anti-Bacterial Agents , Bacterial Proteins/chemistry , Diterpenes , Drug Resistance, Multiple, Bacterial/drug effects , Helicobacter pylori , Lamiaceae/chemistry , Molecular Docking Simulation , Ribosomal Proteins/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Helicobacter pylori/chemistry , Helicobacter pylori/growth & development , HumansABSTRACT
Resveratrol (RV, 3,4',5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype. Furthermore, the combination of radiation with either RV or PSE induced the death of radioresistant PCa cells through delayed repair of radiation-induced DNA double-strand break (DSB) and prolonged G2/M arrest, which induced apoptosis. The administration of RV and PSE effectively enhanced radiation therapy in the shDAB2IP PCa xenograft mouse model. These results demonstrate the promising synergistic effect of RV and PSE combined with radiation in the treatment of radioresistant PCa.
