Multiple modes of cell death in neuroendocrine tumors induced by artesunate.

6533b834fe1ef96bd129cb98

RESEARCH PRODUCT

Multiple modes of cell death in neuroendocrine tumors induced by artesunate.

Madeleine Böckers Thomas A. Efferth Sabine M. Klauck Mona Dawood Matthias M. Weber Ge Yan Christian Fottner

subject

Cyclin-Dependent Kinase Inhibitor p21 Niacinamide Programmed cell death Pharmaceutical Science Artesunate Antineoplastic Agents Apoptosis Neuroendocrine tumors Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Drug Discovery Antineoplastic Combined Chemotherapy Protocols medicine Autophagy Ferroptosis Humans 030304 developmental biology Pharmacology 0303 health sciences Endoplasmic reticulum Phenylurea Compounds Autophagy medicine.disease Endoplasmic Reticulum Stress Neuroendocrine Tumors Complementary and alternative medicine chemistry Cell culture Apoptosis Artesunate 030220 oncology & carcinogenesis Cancer research Molecular Medicine

description

Abstract Background The paucity of effective treatment in neuroendocrine tumors (NETs) encouraged us to investigate the therapeutic value of artesunate (ART) promised by its inhibitory effect against various tumors and broad safety profile. Methods We evaluated the impact of ART on three NET cell lines, BON-1, QGP-1 and NCI-H727 on cellular and molecular levels. Results Our results showed that ART induced endoplasmic reticulum (ER) stress through phosphorylation of eIF2α, which further gave rise to autophagy in all three NET cell lines. Specifically, apoptosis and ferroptosis were also observed in BON-1 cells, which made BON-1 cell line more vulnerable upon ART treatment. The different sensitivities presented on the three cell lines also associated with a differential regulation of p21 on the long run. Co-treatment with p21 inhibitor UC2288 showed an additive effect on QGP-1 and NCI-H727 cell lines indicating p21 upregulation in these two cell lines might confer resistance towards ART treatment. Conclusions It is possible to include ART in the treatment of NETs in the future.

year	journal	country	edition	language
2020-12-01	Phytomedicine : international journal of phytotherapy and phytopharmacology

10.1016/j.phymed.2020.153332 https://pubmed.ncbi.nlm.nih.gov/32957040

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