title: Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria.
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.
authors.affiliation: Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.|Academic Department of Surgery, Royal Free & University College Medical School, Pond Street, London, NW3 2QG, UK.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Sagar
authors.affiliation: Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Sales
authors.affiliation: Department of Clinical Neuroscience, Royal Free & University College Medical School, Pond Street, London, NW3 2QG, UK.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Taanman
authors.affiliation: Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.
authors.forename: Sas
authors.initials: S
authors.lastname: Dijk
authors.affiliation: Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK.|Academic Department of Surgery, Royal Free & University College Medical School, Pond Street, London, NW3 2QG, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Winslet
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