f25, a novel synthetic quinoline derivative, inhibits tongue cancer cell invasion and survival by the PPAR pathway in vitro and vivo.

Tongue cancer has a very high incidence in China, and there is a need to develop new anti-tumour drugs against it. We synthesised 31 novel quinoline derivatives to test their anti-tumour activity. A compound referred to as " f25 " was identified through screening for its high in vitro toxicity against an oral squamous carcinoma cell line (CAL-27). f25 exhibited significant cytotoxicity against CAL-27 cells (IC 50 = 7.70 ± 0.58 μΜ). f25 also inhibited the migration and invasion of CAL-27 cells to a level comparable with that of the chemotherapy agent cisplatin. Moreover, f25 promoted the apoptosis of CAL-27 cells. Transcriptome sequencing and western blotting showed that the mechanism of action of f25 against CAL-27 cells involved the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Specifically, f25 could bind to PPAR-α, PPAR-β, and PPAR-γ and increase their expression. In vivo experiments showed that treatment with f25 led to a reduction in tumour volume in nude mice without significant toxicity. Overall, this study highlights the potential of quinoline compounds (particularly f25) for the design and synthesis of anti-tumour drugs. It also underscores the importance of the PPAR signalling pathway as a target for potential cancer therapies. [Display omitted] • f25 exhibits high cytotoxicity against tongue squamous cell carcinoma cell line CAL-27 cells. • f25 significantly inhibited the migration and invasion of CAL-27 cells and promoted apoptosis. • f25 acts on CAL-27 cells by activating the PPAR signalling pathway thereby exerting an anti-tumour effect. • f25 inhibits tumour growth in a nude mouse model and has a high biosafety profile. [ABSTRACT FROM AUTHOR]