Article ; Online: FTY-720 induces apoptosis in neuroblastoma via multiple signaling pathways.
2017 Volume 8, Issue 66, Page(s) 109985–109999
Abstract: ... The results showed that FTY-720 regulates multiple pathways that result in various effects ... on calcium signaling, ion channel activation and cell survival/death pathways. FTY-720 rapidly inhibits TRPM7 channel ... the effects of FTY-720 or fingolimod, a drug that is FDA-approved for refractory multiple sclerosis, in NB ...
| Abstract | Neuroblastoma (NB) is the most common extra-cranial pediatric solid tumor. High-risk NB is difficult to treat due to the lack of response to current therapies and aggressive disease progression. Despite novel drugs, alternative treatments and multi-modal treatments, finding an effective treatment strategy for these patients continues to be a major challenge. The current study focuses on examining the effects of FTY-720 or fingolimod, a drug that is FDA-approved for refractory multiple sclerosis, in NB. The results showed that FTY-720 regulates multiple pathways that result in various effects on calcium signaling, ion channel activation and cell survival/death pathways. FTY-720 rapidly inhibits TRPM7 channel activity, and inhibited TRPM7 kinase activity, modulates calcium signaling, induces a loss of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore, and ultimately leads to cell death. Interestingly, the data also showed that low concentrations of FTY-720 sensitized drug-resistant NB cells to antineoplastic drugs. These results suggest that FTY-720 may be an attractive alternative for the treatment of NB. |
|---|---|
| Language | English |
| Publishing date | 2017-12-15 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2560162-3 |
| ISSN | 1949-2553 ; 1949-2553 |
| ISSN (online) | 1949-2553 |
| ISSN | 1949-2553 |
| DOI | 10.18632/oncotarget.22452 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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