The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis

0301 basic medicine Drug development Antineoplastic Agents Apoptosis Endoplasmic Reticulum Article Paediatric cancer Inhibitory Concentration 50 Mice Neuroblastoma 03 medical and health sciences Drug Development Cell Line, Tumor Autophagy Animals Humans Isotretinoin Cell Proliferation 0303 health sciences Endoplasmic Reticulum Stress 3. Good health Pancreatic Neoplasms Linoleic Acids Unfolded Protein Response Female Neoplasm Transplantation DNA Damage
DOI: 10.1038/s41419-020-02986-w Publication Date: 2020-09-17T21:38:34Z
ABSTRACT
Neuroblastoma is the leading cause of cancer death in children aged 1 to 4 years. Particularly, five-year overall survival for high-risk neuroblastoma below 50% with no curative options when refractory or relapsed. Most current therapies target cell division and proliferation, thereby inducing DNA damage programmed death. However, aggressive tumours often present alterations these processes are resistant therapy. Therefore, exploring alternative pathways induce tumour will provide new therapeutic opportunities patients. In this study we aimed at testing potential ABTL0812, a novel anticancer drug that induces cytotoxic autophagy eliminate cells, which currently phase II clinical trials adult tumours. Here, show ABTL0812 impaired viability representative lines regardless genetic associated bad prognosis resistance Oral administration mice bearing xenografts growth. Furthermore, our findings revealed that, neuroblastoma, induced via induction endoplasmic reticulum stress, activation unfolded protein response, apoptosis. Remarkably, potentiated antitumour activity chemotherapies differentiating agents such as irinotecan 13-cis-retinoic acid. conclusion, distinctive mechanism action makes it standout be used alone combination
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