SFEBES2016 Poster Presentations Neoplasia, cancer and late effects (18 abstracts)
Metformin alters an anti-proliferative effect of Mitotane in a human adrenocortical cancer (H295R) cell line: preliminary results
Dorota Dworakowska 1, , Paulina Szyszka 2 , Gregory Weitsman 1 , Salvador Diaz-Cano 1 , Marta Korbonits 3 , Ashley Grossman 4 , Stefan Bornstein 1, & Tony Ng 1
1Kings College London, London, UK; 2Medical University of Gdansk, Gdansk, Poland; 3Queen Mary University of London, London, UK; 4OCDEM, Oxford, UK; 5Medical University of Dresden, Dresden, Germany.
Introduction: Metformin is used as a first line treatment in type 2 diabetes. Several studies suggest that patients with type 2 diabetes treated with metformin may have reduced cancer risk. Recently it has been shown that Metformin acts directly on mitochondria to alter cellular bioenergetics and reduce tumorigenesis. We have shown that anti-proliferative effect of Mitotane is related with changes of expression of the genes involved in mitochondrial metabolism in human adrenocortical (H295R), breast, lung and colon cancer (ENDO 2015).
Aim: As both Metformin and Mitotane affect mitochondrial metabolism, the aim of the study was to assess the impact of combine treatment of Metformin and Mitotane on H295R cell line proliferation.
Material and methods: Human adrenocortical cancer cell lines (H295R) were cultured in 96 well plates and cell proliferation rate was assessed by resazurin assay.
Results: Optimum effect of Metformin was observed at 48-h of incubation, resulting in cytotoxicity of 6, 16, 28 and 55% at the concentration of 5, 10, 20 and 40 mM, respectively. Optimum effect of Mitotane (10 μM) was observed at 24-h of incubation, resulting in 30% of cytotoxicity and this concentration was used in combine treatments with Metformin. Even though both compounds inhibited proliferation separately, combine treatment resulted in either total loss of their anti-proliferative effect (Metformin at the concentration of 5 and 10 mM) or significant decrease in cytotoxicity to 9 (P<0.001) and 44% (P<0.001) for Metformin at the concentration of 20 and 40 mM, respectively.
Conclusions: Those preliminary results shows that even though Metformin alone can have an anti-proliferative effect on H295R cell line, it should be added to Mitotane with caution as their combine effect can negatively influence cytotoxic effect of Mitotane. The studies require further experiments.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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