Bergamottin demonstrates preclinical effectiveness against pancreatic cancer by modulating PPAR-γ to induce apoptosis
Cheng Wang1, Linxiao Sun1, Kaixian Deng1
1Department of Laboratory, Guizhou Provincial People's Hospital, Guiyang, China.
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.
Insights
Bergamottin, a natural compound, effectively inhibits pancreatic cancer (PC) progression by reducing cell proliferation, invasion, and migration while inducing apoptosis. This action is mediated through the regulation of the PPAR-γ pathway, showing promise for new PC therapies.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Pancreatic cancer (PC) presents a significant global health challenge due to its high incidence, mortality, and resistance to conventional treatments.
- The urgent need for novel therapeutic strategies necessitates the exploration of natural compounds with anticancer potential.
- Bergamottin, a furanocoumarin from bergamot oil, has shown diverse biological activities, but its specific effects on pancreatic cancer remain underexplored.
Purpose of the Study:
- To investigate the anticancer effects of bergamottin on pancreatic cancer cells.
- To elucidate the underlying molecular mechanism, focusing on the role of Peroxisome proliferator-activated receptor gamma (PPAR-γ) in bergamottin-induced apoptosis.
- To evaluate the therapeutic potential of bergamottin in preclinical pancreatic cancer models.
Main Methods:
- In vitro studies utilized real-time cellular analysis, immunofluorescence, transwell, migration, and flow cytometry assays on PANC-1 and PATU8988 pancreatic cancer cell lines.
- In vivo efficacy was assessed using tumor xenograft models in mice.
- Gene expression profiling via RNA sequencing (RNA-seq) and PPAR-γ inhibition with GW9662 were employed to determine the regulatory mechanism.
Main Results:
- Bergamottin significantly inhibited pancreatic cancer cell proliferation, invasion, and migration in vitro.
- Apoptosis was markedly induced in pancreatic cancer cells treated with bergamottin.
- In vivo studies demonstrated that bergamottin suppressed tumor progression in xenograft models, with RNA-seq revealing alterations in the PPAR signaling pathway, further validated by PPAR-γ inhibition.
Conclusions:
- Bergamottin demonstrates potent anticancer activity against pancreatic cancer by suppressing cell proliferation, invasion, and migration.
- The compound effectively promotes apoptosis in pancreatic cancer cells through the regulation of PPAR-γ.
- These findings highlight bergamottin as a promising candidate for preclinical development as an anti-pancreatic cancer therapeutic agent.
