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Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria

Sagar, J; Sales, K; Taanman, JW; Dijk, S; Winslet, M; (2010) Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria. Cancer Cell International , 10 , Article 31. 10.1186/1475-2867-10-31. Green open access

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Abstract

Background: Colorectal cancer is the third most-common cancer and the second most-common cause of cancer related death in UK. Although chemotherapy plays significant role in the treatment of colorectal cancer, morbidity and mortality due to drug resistance and cancer metastasis are yet to be eliminated. Recently, doxycycline has been reported to have cytotoxic and anti-proliferating properties in various cancer cells. In this study, whether doxycycline was apoptosis threshold lowering agent in colorectal cancer cells by targeting mitochondria was answered.Results: This study showed dose-dependent cytotoxic effects of cisplatin, oxaliplatin and doxycycline in HT29 colorectal cancer cells. Doxycycline showed inhibition of cytochrome-c-oxidase activity in these cells over a time period. The pre-treatment of doxycycline reported statistically significant increased cytotoxicity of cisplatin and oxaliplatin compared to cisplatin and oxaliplatin alone. The caspase studies revealed significantly less expression and activity of caspase 3 in HT29 cells pre-treated with doxycycline compared to the cells treated with cisplatin and oxaliplatin alone.Conclusions: It was concluded that doxycycline lowered the apoptotic threshold in HT 29 cells by targeting mitochondria. This also raised possible caspase-independent mechanisms of apoptosis in HT29 cells when pre-treated with doxycycline however this needs further research work.

Type: Article
Title: Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1475-2867-10-31
Publisher version: http://dx.doi.org/10.1186/1475-2867-10-31
Language: English
Additional information: Amended metadata, uploaded FT (ID 29/11/13)
Keywords: Chemically-modified tetracyclines, in-vitro, doxycycline, proliferation, inhibition, metastasis, invasion, col-3, model
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/142434
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