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FTY-720 induces apoptosis in neuroblastoma via multiple signaling pathways.

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.

SUBMITTER: Lange I

PROVIDER: S-EPMC5746359 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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FTY-720 induces apoptosis in neuroblastoma via multiple signaling pathways.

Lange Ingo I Espinoza-Fuenzalida Italo I Ali Mourad Wagdy MW Serrano Laura Espana LE Koomoa Dana-Lynn T DT

Oncotarget 20171106 66

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, ...[more]

PMID: 29299124

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FTY-720 induces apoptosis in neuroblastoma via multiple signaling pathways.

Publications

FTY-720 induces apoptosis in neuroblastoma via multiple signaling pathways.

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