{"doi":"10.1158/0008-5472.c.6495702","title":"Data from Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth","abstract":"<div>Abstract<p>The effect of the antidiabetic drug metformin on tumor growth was investigated using the paired isogenic colon cancer cell lines HCT116 p53<sup>+/+</sup> and HCT116 p53<sup>−/−</sup>. Treatment with metformin selectively suppressed the tumor growth of HCT116 p53<sup>−/−</sup> xenografts. Following treatment with metformin, we detected increased apoptosis in p53<sup>−/−</sup> tumor sections and an enhanced susceptibility of p53<sup>−/−</sup> cells to undergo apoptosis <i>in vitro</i> when subject to nutrient deprivation. Metformin is proposed to function in diabetes treatment as an indirect activator of AMP-activated protein kinase (AMPK). Treatment with AICAR, another AMPK activator, also showed a selective ability to inhibit p53<sup>−/−</sup> tumor growth <i>in vivo</i>. In the presence of either of the two drugs, HCT116 p53<sup>+/+</sup> cells, but not HCT116 p53<sup>−/−</sup> cells, activated autophagy. A similar p53-dependent induction of autophagy was observed when nontransformed mouse embryo fibroblasts were treated. Treatment with either metformin or AICAR also led to enhanced fatty acid β-oxidation in p53<sup>+/+</sup> MEFs, but not in p53<sup>−/−</sup> MEFs. However, the magnitude of induction was significantly lower in metformin-treated cells, as metformin treatment also suppressed mitochondrial electron transport. Metformin-treated cells compensated for this suppression of oxidative phosphorylation by increasing their rate of glycolysis in a p53-dependent manner. Together, these data suggest that metformin treatment forces a metabolic conversion that p53<sup>−/−</sup> cells are unable to execute. Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin. [Cancer Res 2007;67(14):6745–52]</p></div>","journal":null,"year":2023,"id":404148,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8623,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232805,"name":"Russell G. Jones","orcid":"0000-0003-2250-4675","position":1,"is_corresponding":false},{"id":3837,"name":"Ravi K. Amaravadi","orcid":"0000-0002-5768-2474","position":2,"is_corresponding":false},{"id":883261,"name":"Julian J. Lum","orcid":"0000-0002-5624-3541","position":3,"is_corresponding":false},{"id":262195,"name":"Ralph J. DeBerardinis","orcid":"0000-0002-2705-7432","position":4,"is_corresponding":false},{"id":1182016,"name":"Fangping Zhao","orcid":null,"position":5,"is_corresponding":false},{"id":467352,"name":"Benoı̂t Viollet","orcid":"0000-0002-0121-0224","position":6,"is_corresponding":false},{"id":611838,"name":"Craig B. Thompson","orcid":"0000-0003-3580-2751","position":7,"is_corresponding":false},{"id":1182015,"name":"Monica Buzzai","orcid":null,"position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T01:20:40.264741Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}