Antiproliferative Effects of the Natural Oxadiazine Nocuolin A Are Associated With Impairment of Mitochondrial Oxidative Phosphorylation

Frontiers in Oncology

Oncology

Stig Linder¹  Maria Lígia Sousa²  Vítor Vasconcelos²  Ralph Urbatzka³  Marco Preto³ 

[1] Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institute, Stockholm, Sweden;Department of Medical and Health Sciences, Linköping University, Linköping, Sweden;Faculty of Sciences of University of Porto, Porto, Portugal;Interdisciplinary Centre of Marine and Environmental Research, Porto, Portugal;Interdisciplinary Centre of Marine and Environmental Research, Porto, Portugal;

关键词: natural products;    cyanobacteria;    spheroids;    colon cancer;    anti-cancer drugs;    mitochondria;    autophagy;   

DOI  :  10.3389/fonc.2019.00224

 received in 2018-12-05, accepted in 2019-03-13,  发布年份 2019

来源: Frontiers

【 摘 要 】

Natural products are interesting sources for drug discovery. The natural product oxadiazine Nocuolin A (NocA) was previously isolated from the cyanobacterial strain Nodularia sp. LEGE 06071 and here we examined its cytotoxic effects against different strains of the colon cancer cell line HCT116 and the immortalized epithelial cell line hTERT RPE-1. NocA was cytotoxic against colon cancer cells and immortalized cells under conditions of exponential growth but was only weakly active against non-proliferating immortalized cells. NocA induced apoptosis by mechanism(s) resistant to overexpression of BCL family members. Interestingly, NocA affected viability and induced apoptosis of HCT116 cells grown as multicellular spheroids. Analysis of transcriptome profiles did not match signatures to any known compounds in CMap but indicated stress responses and induction of cell starvation. Evidence for autophagy was observed, and a decrease in various mitochondrial respiration parameter within 1 h of treatment. These results are consistent with previous findings showing that nutritionally compromised cells in spheroids are sensitive to impairment of mitochondrial energy production due to limited metabolic plasticity. We conclude that the antiproliferative effects of NocA are associated with effects on mitochondrial oxidative phosphorylation.

【 授权许可】

Unknown   
Copyright © 2019 Sousa, Preto, Vasconcelos, Linder and Urbatzka.