Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas
| Autor: | Qiang Li, Yi Li, Keiji Kawamoto, Yunbo Zhen, Shiguang Zhao |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Cancer Research Population Notch signaling pathway Down-Regulation Nerve Tissue Proteins Biology medicine.disease_cause Arsenicals Flow cytometry Nestin Mice chemistry.chemical_compound Arsenic Trioxide Intermediate Filament Proteins Western blot In vivo Cell Line Tumor medicine Animals Humans Arsenic trioxide education Mice Inbred BALB C education.field_of_study Receptors Notch medicine.diagnostic_test Brain Neoplasms Oxides Molecular biology Oncology chemistry Cell culture Neoplastic Stem Cells Glioblastoma Carcinogenesis Neoplasm Transplantation Signal Transduction |
| Zdroj: | Cancer Letters. 292:64-72 |
| ISSN: | 0304-3835 |
| Popis: | Cancer stem-like cells (CSLCs) are potential targets for treatment of glioblastoma multiforme (GBM) due to their role in tumorigenesis and recurrence. In this study, we investigated the inhibitory effect of arsenic trioxide (As(2)O(3)) on CSLCs of GBM in human glioma cell lines (U87MG, U251MG and U373MG) in vivo and in vitro. Immunofluorescence staining and flow cytometry revealed that the percentage of Nestin-positive cells in the aforementioned cell lines was diminished by 12%, 14% and 7%, respectively, after treatment with 2 microM As(2)O(3). Furthermore, we used soft-agar in U87MG and tumor xenografts in nude mice to demonstrate the ability of As(2)O(3) to inhibit the formation of tumor in the three cell lines. These results indicate the negative regulation of CSLCs by As(2)O(3). In addition, a Western blot analysis revealed decreased levels of Notch1 and Hes1 proteins due to As(2)O(3) treatment. We conclude that As(2)O(3) has a remarkable inhibitory effect on CSLCs in glioma cell lines in vivo and in vitro; in addition, we determined that the mechanism of CSLC inhibition involves the deregulation of Notch activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect