This study aimed to evaluate the anti-
pancreatic cancer effects of
flavonoids in Plumula Nelumbinis. High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry showed that
apiin,
rhoifolin, and
vitexin were three principal components in total
flavonoids derived from Plumula Nelumbinis, with
vitexin being the most abundant component. Cell viability assay revealed that
apiin,
rhoifolin, and
vitexin could inhibit proliferation of PANC-1 and ASPC-1, with
rhoifolin showing the maximum inhibitory effect.
Rhoifolin inhibited cell proliferation and promoted apoptosis of
pancreatic cancer cells, which was associated with up-regulated JNK and p-JNK as well as down-regulated p-AKT.
Rhoifolin also inhibited cell migration and invasion, and increased the
antioxidant capacity in PANC-1 and ASPC-1. Besides, AKT activator (SC79) or JNK inhibitor (
SP600125) effectively reversed the anticancer effects of
rhoifolin in
pancreatic cancer. Quantitative proteomics analysis showed that
rhoifolin altered proteomic profiles in
pancreatic cancer cells. Western blot analysis showed that
rhoifolin down-regulated
transforming growth factor beta 2 (TGF-β2), the regulator of
proteoglycan synthesis, with the concomitant down-regulation of phosphorylated SMAD family member 2 (SMAD2), the downstream effector of TGF-β2. In conclusion,
rhoifolin regulates the AKT/JNK/
caspase-3 and TGF-β2/SMAD2 signaling pathways, which may contribute to its anti-
pancreatic cancer effects.