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Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironmentsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Zhang Xiaonan, Fryknäs Mårten, Hernlund Emma, Fayad Walid, Milito Angelo De, Olofsson Maria Hägg, Gogvadze Vladimir, Dang Long, Påhlman Sven, Schughart Leoni A.Kunz, Rickardson Linda, D$\prime$Arcy Padraig, Gullbo Joachim, Nygren Peter, Larsson Rolf, Linder Stig
- Журнал: Nature communications
- Том: 5
- Год издания: 2014
- Издательство: Nature Pub. Group
- Местоположение издательства: United Kingdom
- DOI: 10.1038/ncomms4295
- Аннотация: 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.
- Добавил в систему: Гогвадзе Владимир Георгиевич