Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways |
| |
Authors: | Kim Su-Hwa Bae Hyun Cheol Park Eun-Jung Lee Chae Ryun Kim Byung-Joo Lee Sanghoon Park Hyun Ho Kim Sung-Joon So Insuk Kim Tae Woo Jeon Ju-Hong |
| |
Institution: | aDepartment of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA;bDepartment of Pharmacology, School of Pharmacy, Soochow University, Jiangsu Province, China |
| |
Abstract: | Elongation factor-2 kinase (eEF-2 kinase, also known as calmodulin-dependent protein kinase III), is a unique calcium/calmodulin-dependent enzyme that inhibits protein synthesis by phosphorylating and inactivating elongation factor-2 (eEF-2). We previously reported that expression/activity of eEF-2 kinase was up-regulated in several types of malignancies including Gliomas, and was associated with response of tumor cells to certain therapeutic stress. In the current study, we sought to determine whether eEF-2 kinase expression affected sensitivity of glioma cells to treatment with tumor the necrosis factor-related apoptosis-inducing ligand (TRAIL), a targeted therapy able to induce apoptosis in cancer cells but causes no toxicity in most normal cells. We found that inhibition of eEF-2 kinase by RNA interference (RNAi) or by a pharmacological inhibitor (NH125) enhanced TRAIL-induced apoptosis in the human glioma cells, as evidenced by an increase in apoptosis in the tumor cells treated with eEF-2 kinase siRNA or the eEF-2 kinase inhibitor. We further demonstrated that sensitization of tumor cells to TRAIL was accompanied by a down-regulation of the anti-apoptotic protein, Bcl-xL, and that overexpression of Bcl-xL could abrogate the sensitizing effect of inhibiting eEF-2 kinase on TRAIL. The results of this study may help devise a new therapeutic strategy for enhancing the efficacy of TRAIL against malignant glioma by targeting eEF-2 kinase. |
| |
Keywords: | eEF-2 kinase TRAIL Bcl-xl Apoptosis Glioblastoma |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|