Inhibition of pancreatic cancer cells by furocoumarins from Poncirus trifoliata

Texas A&M University, College Station, TX 77845–2119.

Poncirus trifoliata (syn. Citrus trifoliata), is a member of Rutaceae family. Fruits of Poncirus trifoliata (trifoliata orange) are well known for traditional medicines in Asia especially for treating allergic diseases, inflammation, ulcers, anti HIV-1 and hepatoxicity. In the present study, lyophilized trifoliata oranges were extracted with chloroform and dried extract was fractionated on flash chromatography to obtain four compounds. The purity of the compounds were analyzed by HPLC and identified by 1D, 2D NMR spectral data as bergamottin, imperatorin, isoimperatorin and epoxyimperatorin. These compounds were tested for inhibitory activity of pancreatic cancer (Panc-28) in culture models. Among the tested compounds, epoxyimperatorin was found to exhibit highest proliferation inhibition (35%) of cells at 12.5µM after incubation of 24h and more than 80% cells were inhibited after 72h treatment with 50µM. The magnitude of proliferation inhibition was followed by imperatorin and bergamottin. Studies on expression of protein by immunoblotting demonstrate that furocoumarins of Poncirus trifoliate are capable of inducing apotosis through activation of caspase-3, Bax/bcl₂, death inducing protein (p53) and caspase-8. The magnitude and nature of cytotoxicity of activity suggest that both epoxyimperatorin and imperatorin may have greater potency and it is worth exploring their mechanism using in vivo system. The present research is based on work supported by the “Designing Foods for Health” through USDA NIFA # 2010–34402–20875.