Does Doxycycline work in synergy with cisplatin and oxaliplatin in colorectal cancer?
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Does Doxycycline work in synergy with cisplatin and oxaliplatin in colorectal cancer? Jayesh Sagar*1,2, Kevin Sales1, Sas Dijk1, JanWillem Taanman3, Alexander Seifalian2 and Mark Winslet1,2 Address: 1Division of Surgery and Interventional Science, University College London, Gower Street, London, WC1E 6BT, UK, 2Academic Department of Surgery, Royal Free & University College Medical School, Pond Street, London, NW3 2QG, UK and 3Department of Clinical Neuroscience, Royal Free & University College Medical School, Pond Street, London, NW3 2QG, UK Email: Jayesh Sagar* - [email protected]; Kevin Sales - [email protected]; Sas Dijk - [email protected]; JanWillem Taanman - [email protected]; Alexander Seifalian - [email protected]; Mark Winslet - [email protected] * Corresponding author
Published: 6 January 2009 World Journal of Surgical Oncology 2009, 7:2
doi:10.1186/1477-7819-7-2
Received: 16 May 2008 Accepted: 6 January 2009
This article is available from: http://www.wjso.com/content/7/1/2 © 2009 Sagar et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: In recent years, apart from antibacterial properties, doxycycline is reported to have cytotoxic and anti-proliferative actions in various cancers including colorectal cancer. Colorectal cancer constitutes one of the most common cancers in the western population. Apart from surgery, chemotherapy plays crucial role in the treatment of colorectal cancer. Cisplatin and oxaliplatin are most commonly used platinum compounds for the cancer chemotherapy. This study has looked for any impact of doxycycline on the cytotoxic effects of platinum compounds in colorectal cancer including its mechanisms of actions. Methods: HT 29 colorectal cancer cells were used for this study. These cells were treated with cisplatin and oxaliplatin with or without doxycycline treatment. The caspase 3 gene expression was quantitated by gel electrophoresis and qualitated by real time polymerase chain reactions. The caspase 3 activity was assessed in HT 29 cells with fluorescence kit. Results: The results revealed increased caspase 3 gene expressions and activities in HT 29 cells treated with cisplatin, oxaliplatin and doxycycline; however the combination of doxycycline with cisplatin and oxaliplatin did not report increased caspase 3 gene expressions and activity compared to cisplatin and oxaliplatin alone. Conclusion: We concluded that doxycycline has role in apoptosis induction in the colorectal cancer. However, it did not show any synergy with platinum compounds in the colorectal cancer cells. This study also pointed towards possible caspase-independent actions of doxycycline with cisplatin and oxaliplatin. However, further work is required to underpin the
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