Alterations in the omics profiles in mevalonate pathway-inhibited cancer cells

• Published in: Life sciences (1973) 2023-01, Vol.312, p.121249-121249, Article 121249
• Main Authors: Warita, Tomoko, Irie, Nanami, Zhou, Yaxuan, Tashiro, Jiro, Sugiura, Akihiro, Oltvai, Zoltán N., Warita, Katsuhiko
• Format: Article
• Language: English
• Subjects: Atorvastatin - pharmacology; Cancer cells; Glycolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Metabolome; Mevalonic Acid; Neoplasms - drug therapy; Neoplasms - genetics; Polyamine metabolism; Polyamines; Purines; Statins; Transcriptome
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.121249

Statins, cholesterol-lowering drugs, are potential therapeutic agents for inhibiting cancer proliferation. However, the mechanisms that mediate the effects of statins, the homeostatic responses of tumor cells to statin therapy, and the modes underlying the antitumor effects of statins remain unclear. To uncover the effects of statins on cancer cells in vitro, we performed transcriptome and metabolome analyses on atorvastatin-treated statin-resistant and statin-sensitive lung cancer cells. The results of Gene Ontology terms and pathway enrichment analyses showed that after 24 h of atorvastatin treatment, the expression of cell cycle- and DNA replication-related genes was significantly decreased in the statin-sensitive cancer cells. The results of metabolome analysis showed that the components of polyamine metabolism and purine metabolism, glycolysis, and pentose phosphate pathway were decreased in the statin-sensitive cancer cells. Differences in cellular properties between statin-sensitive and statin-resistant cancer cells revealed additional candidates for therapeutic targets in statin-treated cancer cells and suggested that inhibiting these metabolic pathways could improve efficacy. In conclusion, combining statins with inhibitors of polyamine metabolism (cell proliferation and protein translation), purine metabolism (DNA synthesis), glycolytic system (energy production), and pentose phosphate pathway (antioxidant stress) might enhance the anticancer effects of statins. •Atorvastatin lowers DNA replication in statin-sensitive cancer cells.•Atorvastatin affects glycolytic/purine/polyamine metabolism in cancer cells.•Inhibiting identified metabolic pathways may raise anticancer effects of statins.•Our findings are valuable for developing novel statin-based cancer treatments.