Evaluating the role of Metformin on DNA damage and DNA damage response in ovarian cancer

Konstantinou, Timothea (2014). Evaluating the role of Metformin on DNA damage and DNA damage response in ovarian cancer. University of Birmingham. M.Res.

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Abstract

Ovarian cancer is one of the most common and lethal types of cancer among women. The increased mortality rate reflects the need for discovery of new therapeutic venues. The anti-diabetic drug Metformin has started to show anti-cancer potential as epidemiological studies have associated its long-term use with reduced risk of ovarian cancer and increased survival for ovarian cancer patients. However, the underlying mechanisms of Metformin’s effects are not well understood, especially its association with DNA damage which remains controversial. In this study, we evaluated the role of Metformin in DNA damage and DNA damage response in two ovarian cancer cell lines. Immunofluorescence experiments and colony formation assays suggest that Metformin potentiated the DNA-damaging effects of irradiation as it delayed the resolution of protein foci associated with DNA double-strand breaks and reduced cell survival respectively. Furthermore, Metformin had a greater effect in replicating cells and increased the cytotoxic effects of the nucleoside analog Gemcitabine. Thus, our data suggest that Metformin may delay or impair the DNA damage response and may have a stronger effect during replication. However, further studies are essential for verification and discovery of the underlying mechanisms of Metformin in the DNA damage response in ovarian cancer.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

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