Bergamottin demonstrates preclinical effectiveness against pancreatic cancer by modulating PPAR-γ to induce apoptosis

Background: Pancreatic cancer (PC) has escalating incidence and mortality rates, with poor prognosis and resistance to traditional therapies, highlighting the urgent need for new drug development. Bergamottin, a natural furanocoumarin from bergamot oil, has diverse biological activities, but its anticancer effects on PC remain scarce and limited. This study aimed to investigate the anticancer properties of bergamottin in PC and elucidate the regulatory mechanism of PPAR-γ in inducing apoptosis.

Methods: In vitro, real-time cellular analysis (RTCA), immunofluorescence, transwell assay, migration assay, and flow cytometry were used to assess bergamottin’s effects on proliferation, migration, invasion, and apoptosis of PANC-1 and PATU8988 cells. In vivo, tumor xenograft experiments were conducted to verify its anticancer effect. RNA sequencing (RNA-seq) analyzed gene expression changes in PANC-1 cells before and after bergamottin intervention. PPAR-γ inhibition (GW9662) was used to validate the mechanism.

Results: Bergamottin significantly inhibited proliferation, invasion, and migration of PANC-1 and PATU8988 cells, and induced their apoptosis in vitro; it also suppressed PC progression in xenograft mouse models. RNA-seq identified 317 up-regulated and 111 down-regulated differentially expressed genes (DEGs), with functional analysis suggesting involvement of the PPAR signaling pathway. Validation via PPAR-γ inhibitor confirmed the regulatory role of PPAR-γ.

Conclusions: Bergamottin effectively suppresses PC cell proliferation, invasion, and migration, and promotes apoptosis by regulating PPAR-γ. These findings suggest that bergamottin exhibits promising preclinical anti-tumor activity against PC.