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Effect of Lipoic Acid on the Biochemical Mechanisms of Resistance to Bortezomib in SH-SY5Y Neuroblastoma Cells.

Abstract：

:Neuroblastoma (NB) is an extracranial solid cancer and the most common cancer in infancy. Despite the standard treatment for NB is based on the combination of chemotherapeutic drugs such as doxorubicin, vincristine, cyclophosphamide, and cisplatin, chemoresistance occurs over the time. The aim of the present research was to evaluate the effect of bortezomib (BTZ) (50 nM) on NB cell viability and how lipoic acid (ALA) (100 μM) modifies pharmacological response to this chemotherapeutic agent. Cell viability was assessed by ATP luminescence assay whereas expression of oxidative stress marker (i.e., heme oxygenase-1) and endoplasmic reticulum stress proteins was performed by real-time PCR, western blot, and immunofluorescence. Our data showed that BTZ treatment significantly reduced cell viability when compared to untreated cultures (about 40%). Interestingly, ALA significantly reduced the efficacy of BTZ (about 30%). Furthermore, BTZ significantly induced heme oxygenase-1 as a result of increased oxidative stress and such overexpression was prevented by concomitant treatment with ALA. Similarly, ALA significantly reduced BTZ-mediated endoplasmic reticulum stress as measured by reduction in BiP1 and IRE1α, ERO1α, and PDI expression. In conclusion, our data suggest that BTZ efficacy is dependent on cellular redox status and such mechanisms may be responsible of chemoresistance to this chemotherapeutic agent.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Tibullo D,Giallongo C,Puglisi F,Tomassoni D,Camiolo G,Cristaldi M,Brundo MV,Anfuso CD,Lupo G,Stampone T,Li Volti G,Amenta F,Avola R,Bramanti V

doi

10.1007/s12035-017-0575-6

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

3344-3350

issue

4

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-017-0575-6

journal_volume

55

pub_type

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