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Antiproliferative Effects of the Natural Oxadiazine Nocuolin A Are Associated With Impairment of Mitochondrial Oxidative Phosphorylation
Univ Porto, Portugal; Interdisciplinary Ctr Marine and Environm Res, Portugal.
Interdisciplinary Ctr Marine and Environm Res, Portugal.
Univ Porto, Portugal; Interdisciplinary Ctr Marine and Environm Res, Portugal.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.ORCID iD: 0000-0002-4952-445X
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2019 (English)In: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, article id 224Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 9, article id 224
Keywords [en]
natural products; cyanobacteria; spheroids; colon cancer; ant-cancer drugs; mitochondria; autophagy
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-156561DOI: 10.3389/fonc.2019.00224ISI: 000463427000001PubMedID: 31001482OAI: oai:DiVA.org:liu-156561DiVA, id: diva2:1315872
Note

Funding Agencies|Structured Program of R&D&I INNOVMAR-Innovation and Sustainability in the Management and Exploitation of Marine Resources - Northern Regional Operational Program (NORTE2020) through the European Regional Development Fund (ERDF) [NORTE-01-0145-FEDER-000035]; project CYANCAN-Uncovering the cyanobacterial chemical diversity: the search for novel anticancer compounds - NORTE 2020, Portugal 2020 [PTDC/MEDQUI/30944/2017]; European Union through the ERDF; Foundation for Science and Technology; FCT [SFRH/BPD/112287/2015, SFRH/BD/108314/2015]

Available from: 2019-05-15 Created: 2019-05-15 Last updated: 2019-10-25

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