Inhibition of JNJ-26481585-mediated autophagy induces apoptosis via ROS activation and mitochondrial membrane potential disruption in neuroblastoma cells

Molecular and Cellular Biochemistry
Vamsi Krishna KommalapatiAnjana Devi Tangutur

Abstract

Neuroblastoma (NB) is the common pediatric tumor of the sympathetic nervous system characterized by poor prognosis. Owing to the challenges such as high tumor heterogeneity, multidrug resistance, minimal residual disease, etc., there is an immediate need for exploring new therapeutic strategies and effective treatments for NB. Herein, in the current study, we explored the unexplored response of NB cells to the second-generation histone deacetylase inhibitor (HDACi) JNJ-26481585(JNJ) and the lysosomotropic agent, Chloroquine (CQ) alone and upon JNJ/CQ treatment as a plausible therapeutic. We identify that while JNJ alone induced autophagy in NB cells, JNJ/CQ treatment decreased the viability and proliferation of NB cells in vitro by switching from autophagy to apoptosis. Further we found that autophagy inhibition by CQ pre-treatment led to the generation of ROS and a decrease in the mitochondrial membrane potential (MMP) that subsequently caused caspase-3-mediated apoptotic cell death in NB cells. Corroborating the above observations, we found that the ROS scavenger N-acetylcysteine (NAC) countered caspase-3 activity and the cells were rescued from apoptosis. Finally, these observations establish that JNJ/CQ treatment resulted i...Continue Reading

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Citations

May 1, 2021·Neoplasia : an International Journal for Oncology Research·María Ovejero-SánchezAna Belén Herrero
Jun 15, 2021·Molecular Biology Reports·Vamsi Krishna KommalapatiAnjana Devi Tangutur
Aug 12, 2021·Journal of Medicinal Chemistry·Yang LiLiang Ouyang

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Methods Mentioned

BETA
fluorescence microscopy

Software Mentioned

ImageJ
Image J
GraphPad Prism

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