Reducing Dietary Protein Enhances the Anti-tumor Effects of Chemotherapy

ABSTRACT: Diet is believed to be an important mediator of oncogenesis and response to anti-cancer therapies, although, no evidence-based dietary guidelines exist for patients with cancer. Limiting protein intake can suppress tumor growth by both inducing nutrient stress and enhancing anti-tumor immunity. However, little is known about the impact of reducing dietary protein on the efficacy of standard anti-cancer therapies, including chemotherapy. Here, we present evidence that reducing protein intake in mice by 50% essentially stops the growth of established tumors, in parallel with inducing a stress response and DNA damage. Further, a reduced protein diet markedly enhances tumor regression upon treatment with 5-fluorouracil (5-FU), accompanied by elevated apoptosis and suppressed mitosis of tumor cells. Proteomic analysis of tumors from 5-FU treated mice fed control or reduced protein diets revealed marked changes including decreased abundance of proteins that mediate DNA repair and replication in mice given diet with reduced protein. In vitro studies mimicking amino acid changes found in tumors from reduced protein-fed mice revealed that cell viability and proliferation rates were similar irrespective of amino acid levels in medium, following 5-FU treatment. In contrast, cGAS-STING signaling, including transcription of Interferon beta 1, was maximally increased in 5-FU treated cells cultured in modified amino acid medium. These findings correlated with enhanced immune cell influx into tumors from mice fed reduced protein diet following 5-FU administration. Collectively, these findings suggest that reducing dietary protein in cancer patients may enhance the efficacy of chemotherapy, which may be mediated by anti-tumor immunity.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver Cancer Cell

DISEASE(S): Liver Cancer

SUBMITTER: Alex Montoya  

LAB HEAD: Dr Pavel Shliaha

PROVIDER: PXD052110 | Pride | 2025-03-07

REPOSITORIES: Pride