Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Xiaonan Zhang, Mårten Fryknäs, Emma Hernlund, Walid Fayad, Angelo De Milito, Maria Hägg Olofsson, Vladimir Gogvadze, Long Dang, Sven Påhlman, Leoni A. Kunz Schughart, Linda Rickardson, Padraig D′Arcy, Joachim Gullbo, Peter Nygren, Rolf Larsson, Stig Linder

ABSTRACT

Abnormal vascularization of solid tumours results in the development of microenvironments deprived of oxygen and nutrients that harbour slowly growing and metabolically stressed cells. Such cells display enhanced resistance to standard chemotherapeutic agents and repopulate tumours after therapy. Here we identify the small molecule VLX600 as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues. The anticancer activity is associated with reduced mitochondrial respiration, leading to bioenergetic catastrophe and tumour cell death. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation. Importantly, VLX600 displays tumour growth inhibition in vivo. Our findings suggest that tumour cells in metabolically compromised microenvironments have a limited ability to respond to decreased mitochondrial function, and suggest a strategy for targeting the quiescent populations of tumour cells for improved cancer treatment. More... »

PAGES

3295

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms4295

DOI

http://dx.doi.org/10.1038/ncomms4295

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012712523

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24548894


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