Metformin Administration to Glucose-restricted Cells Attenuates PKA Signaling in S. cerevisiae

Recent research in cancer treatment points to metformin, a drug for type 2 diabetes, as a potential anti-cancer therapeutic, as well as carbon limitation as a dietary measure. A new study, investigating effects of metformin treatment on colorectal cancer cells, pointed to the fact that response to metformin treatment depended on extracellular glucose concentration. That is why in the current study, effects of both carbon limitation and metformin treatment are explored via transcriptomics analyses. It is demonstrated that cells grown in glucose-limited and metformin treated medium had the highest variance according to transcriptional profiles, compared to individual treatments. Metformin administration, when combined with glucose restriction, downregulates proliferative pathways such as transcription initiation and ribosome biogenesis while upregulates energy derivation and autophagic mechanisms. Enrichment analyses point to an attenuated cAMP-PKA signaling pathway in the cells grown in combined treatment medium. It is proposed that combined treatment exerts its beneficial effect on this pathway, since cAMP-PKA signaling may be a potential target for pharmacological treatment of tumors.