Hexafluoro-2-propanol represses colorectal cancer proliferation by regulating transaminases

Hexafluoro-2-propanol (HFIP) is a metabolite of sevo-flurane used as part of the general anaesthesia tech-nique. This study aims to investigate the effect of HFIP in colorectal cancer (CRC) and the regulation of associ-ated genes. The differential expressed genes (DEGs) with HFIP treatment were analysed based on GEO dataset GSE56256. Due to the restricted number of studies per-forming RNA-Seq in CRC with HFIP treatment, we se-lected a CRC patient cohort (GSE23878) to obtain DEGs that were compared with DEGs from GSE56256. The DEGs with opposite expression patterns in these two GEO datasets indicate that the genes mediate the func-tion of HFIP, thereby repress the progression of CRC. The DEGs from these two GEO datasets were analysed independently. We obtained 10 up-regulated genes in GSE23878 (CRC patient cohort) were also down-regulat-ed in GSE56256 (HFIP cohort), therefore, these 10 genes may function as tumor suppressors in CRC and may be involved in the function of HFIP. STRING analysis dem-onstrated an interaction in GPT2, PSAT1 and SLC7A11. The high expression of GPT2, PSAT1 and SLC7A11 were confirmed in TCGA-COAD datasets and in CRC cells. HFIP treatment repressed GPT2, PSAT1 and SLC7A11, which resulted in an inhibited proliferation and colony forma-tion ability of DLD-1 and HCT-116 cells. Silencing GPT2, PSAT1 and SLC7A11 showed similar effect compared to HFIP treatment. Overexpression of GPT2, PSAT1 and SLC7A11 abrogated the effect of HFIP. In conclusion, the sevoflurane metabolite HFIP plays a cancer suppression role depending on cell proliferation in colorectal can-cer through the down-regulation of GPT2, PSAT1 and SLC7A11 expression.