In previous work we observed conditions in which growth was inhibited but glucose metabolism was increased in cancer cells incubated with the biguanide, phenformin. One of the postulated mechanisms of action of biguanides is the inhibition of Complex I in the mitochondrial electron transport chain. Rotenone is a classical inhibitor of Complex I. In the present work we sought to determine if phenformin and rotenone would exert similar actions on growth and glucose metabolism of colon and bladder cancer cells in vitro. A concentration-dependent inhibition of growth was observed when cells were incubated with rotenone. Glucose metabolism, as judged by a decrease in glucose concentration and an increased acidification of the medium, revealed a biphasic response to rotenone. An initial increase in glucose metabolism at lower concentrations of rotenone was followed by a decreasing glucose metabolism at high concentrations of the drug. The response to rotenone showed a pattern similar to that observed with cells treated with phenformin. However, the actions of rotenone were seen at concentrations approximately a thousand fold less than with phenformin. The data obtained provide further support for the hypothesis that actions of phenformin on cancer cells may be mediated through inhibitory effects on Complex I of the mitochondrial electron transport system.

Phenformin and rotenone can increase glucose metabolism while inhibiting growth in colon and bladder cancer cells

252nd National Meeting (2016)

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