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