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

Molecular Neurobiology
Daniele TibulloVincenzo Bramanti

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...Continue Reading

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Citations

Jun 28, 2018·Molecular Neurobiology·Ignazio BarbagalloDaniele Tibullo
Jul 6, 2017·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Daniele TibulloVincenzo Bramanti
May 1, 2021·Frontiers in Molecular Biosciences·Shulong CaoHaiyuan Zhang
May 28, 2021·Bioorganic & Medicinal Chemistry Letters·Patamawadee SilalaiRungnapha Saeeng
Aug 23, 2021·Molecular Biology Reports·Panagiotis Theodosis-NobelosEleni A Rekka

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Methods Mentioned

BETA
PCR
Infrared Imaging
nuclear translocation

Software Mentioned

Prism
ATPLite
Graphpad Prism

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