Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.
(2014) In Nature Communications 5(Feb 18).- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4334498
- author
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 5
- issue
- Feb 18
- article number
- 3295
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:24548894
- wos:000332667600042
- scopus:84894542141
- pmid:24548894
- ISSN
- 2041-1723
- DOI
- 10.1038/ncomms4295
- language
- English
- LU publication?
- yes
- id
- e48e8c48-53bc-4543-a474-bd0e5084d4a0 (old id 4334498)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24548894?dopt=Abstract
- date added to LUP
- 2016-04-01 12:54:35
- date last changed
- 2022-03-29 04:27:13
@article{e48e8c48-53bc-4543-a474-bd0e5084d4a0, 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.}}, author = {{Zhang, Xiaonan and Fryknäs, Mårten and Hernlund, Emma and Fayad, Walid and De Milito, Angelo and Olofsson, Maria Hägg and Gogvadze, Vladimir and Dang, Long and Påhlman, Sven and Schughart, Leoni A Kunz and Rickardson, Linda and D Arcy, Padraig and Gullbo, Joachim and Nygren, Peter and Larsson, Rolf and Linder, Stig}}, issn = {{2041-1723}}, language = {{eng}}, number = {{Feb 18}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.}}, url = {{http://dx.doi.org/10.1038/ncomms4295}}, doi = {{10.1038/ncomms4295}}, volume = {{5}}, year = {{2014}}, }