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
AUTHORS (18)
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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