Impact of physiological media on acute myeloid leukemia bioenergetics and cell proliferation

Increasing emphasis has been placed on improving the physiological relevance of cell culture media with formulations such as Human Plasma-Like Medium (HPLM). Given that shifts in mitochondrial metabolism and nutrient use are emerging as anti-cancer targets, the present study sought to investigate the impact of culture media formulation on mitochondrial bioenergetics and cancer cell growth. To do this, we used acute myeloid leukemia (AML) cells and compared acute and chronic effects of HPLM versus different supraphysiological medias. The AML mitochondrial phenotype was largely unaffected by exposure to either physiological or supraphysiological medias, establishing that the key features of AML mitochondria remain phenotypically stable under diverse nutrient conditions and proliferation rates. Both acute and chronic culturing in HPLM slowed AML cell proliferation. However, merely identifying and supplementing single nutrients that were deficient in HPLM did not improve proliferation and was not sufficient to pinpoint actionable fuel preferences. Transferring cells back to native Iscove's Modified Dulbecco's Medium (IMDM) media immediately restored the proliferative phenotype, suggesting responsiveness to the entirety of the nutrient environment. Supraphysiological culture medias other than IMDM were all characterized by slower proliferation; however, none were associated with changes in cell viability, demonstrating that the native culture medium is optimal if the experimental aim is maximal growth. Despite Dulbecco's Modified Eagle Medium (DMEM) being similar in nutrient composition to IMDM and categorized as supraphysiological, both acute and chronic culturing in DMEM resulted in slower growth, akin to what was observed with HPLM. Altogether, independent of growth, AML mitochondria remain largely unperturbed by changes in the culture media, and rather than specific nutrients or physiological relevance, AML cell proliferation is influenced by the complete nutrient profile.