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

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Sousa, ML (Author) Other; Preto, M (Author) Other; Vitor Vasconcelos (Author) FCUP; Linder, S (Author) Other; Urbatzka, R (Author) Other

Journal

Title: Frontiers in Oncology

Vol. 9

ISSN: 2234-943X

Publisher: Frontiers Media

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00Q-EG3

DOI: 10.3389/fonc.2019.00224

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13