Analysis Of The Metabolism Of Ketone Bodies And Lactate By Gastrointestinal Tumour Cells In Vitro

Purpose: The effect of a ketogenic diet on tumour growth is currently controversial. For this study we analysed tumour cells in vitro to determine what level of oxygen is required for the oxidative degradation of ketone bodies (beta-hydroxybutyrate) and the metabolites glucose and lactate that are also present in a ketogenic diet. In addition, tumour growth was examined under a standard ketogenic diet in an animal model.Material and Methods: Six different gastrointestinal tumour cell lines grown to confluence were investigated in vitro for their metabolic properties at 21% and 1% oxygen. Concentrations of glucose, lactate, and beta-hydroxybutyrate were quantified using standard enzymatic assays. A ketosis was induced in nude mice via a standardised ketogenic diet and tumour growth was induced by subcutaneously injected tumour cells.Results: Cell cultures of the 6 tumour cell lines were able to metabolize ketone bodies as well as lactate at 21% oxygen, but not at 1%. Glucose, in contrast, was metabolized at both oxygen concentrations by all 6 tumour cell lines. The data indicate that tumour cells with access to both glucose and lactate at 21% oxygen, consume glucose first and only when glucose is exhausted, do they start to metabolise lactate. Mice fed a ketogenic diet represent a clear physiological ketosis with elevated blood ketone levels. Tumours in the ketogenic diet group grew slower and had lower intratumoral lactate levels in comparison to tumours in the standard diet group.Conclusion: The in vitro data presented support the concept that metabolism in solid tumours is significantly influenced by the local oxygenation. Oxygen concentrations of 1%, usually found in solid tumours (tumour hypoxia), are insufficient for the in vitro metabolization of ketone bodies and lactate in tumour cell lines, in contrast to glucose that is metabolized under these conditions. Therefore, a therapeutic approach that targets the tumour cell energy metabolism under hypoxic conditions must inhibit glucose metabolism pharmacologically with decreased glucose supply, e.g. via dietary interventions.