BERKELEY, CA (UroToday.com) - Recently, we have shown that metformin exploits its anti-proliferative effect in prostate cancer cells by reducing glucose oxidation through complex I inhibition. At the same time, prostate cancer cells in vitro and in vivo counteract the reduced availability of glucose-derived carbon in the tricarboxylic acid cycle by fueling the proliferation relevant fatty acids synthesis pathway with glutamine-derived carbon. This finding implies that, specifically, cancer cells with high levels of glucose oxidation and low glutamine metabolism are susceptible towards a metformin therapy.
This is specifically interesting for prostate cancer since upon an oncogenic transformation of the prostate, aconitase is reactivated, leading to increased citrate oxidation. Moreover, prostate cancer cells display high rates of de novo lipid synthesis, which increases their dependency on glutamine-derived carbon for fatty acid synthesis upon metformin treatment. Thus, combining metformin with an inhibitor of glutamine metabolism showed highly synergistic effects on cell proliferation in vitro and could be a potent way to treat prostate cancer in vivo.
Written by:
Sarah-Maria Fendt, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA USA
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