Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA

Serena Vella, Ilaria Penna, Luca Longo, Giulia Pioggia, Patrizia Garbati, Tullio Florio, Fabio Rossi, Aldo Pagano

Research output: Contribution to journalArticle

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Abstract

High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In a recent study, we demonstrated that in vitro and in vivo over-expression of the non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB cell differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced by NDM29 is characterized by decrease of the expression of ABC transporters responsible for anticancer drug resistance. Thus, the pharmacological induction of NDM29, in principle, might represent a possible novel strategy to increase cytotoxic drug responses. In this work, we identify a small molecule able to induce the expression of NDM29 in NB cells, conferring to malignant cells increased susceptibility to cisplatin cytotoxic effects. We demonstrate that the pharmacological induction of NDM29 expression in vivo enhances the antitumoral effects of chemotherapy specifically on tumour initiating/cancer stem cells sub-population, usually refractory to therapies and responsible for tumour relapse. In summary, we suggest a novel therapeutical approach possibly useful to treat very aggressive NB cases with poor prognosis. This novel pharmacological strategy aims to promote differentiation of "stem-like" cells to render them more susceptible to the killing action of cytotoxic anticancer drugs.

Original languageEnglish
Article number18144
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Dec 17 2015

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Differentiation Antigens
Neuroblastoma
Cisplatin
Neoplasms
Pharmacology
Untranslated RNA
ATP-Binding Cassette Transporters
Neoplastic Stem Cells
Drug Resistance
Pharmaceutical Preparations
perhexiline maleate
Cell Differentiation
Stem Cells
Pediatrics
Phenotype
Gene Expression
Recurrence
Drug Therapy
Population

ASJC Scopus subject areas

  • General

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Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA. / Vella, Serena; Penna, Ilaria; Longo, Luca; Pioggia, Giulia; Garbati, Patrizia; Florio, Tullio; Rossi, Fabio; Pagano, Aldo.

In: Scientific Reports, Vol. 5, 18144, 17.12.2015.

Research output: Contribution to journalArticle

Vella, Serena ; Penna, Ilaria ; Longo, Luca ; Pioggia, Giulia ; Garbati, Patrizia ; Florio, Tullio ; Rossi, Fabio ; Pagano, Aldo. / Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA. In: Scientific Reports. 2015 ; Vol. 5.
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