Dietary approach to attenuate human pancreatic cancer growth and migration with innoxiousness

- Extract of εCUP shows in vitro anti-cancer effects.
- The extract regulates the intracellular signaling of human pancreatic cancer cells.
- Extract lacking hesperidin and narirutin has no pro-angiogenic effect in HUVECs.
- Extract lacking hesperidin and narirutin inhibits pancreatic cancer growth in vivo.

Pancreatic cancer is one of the most dangerous cancers. Despite many efforts to improve the prognosis of pancreatic cancer patients, limited progress has been made. In this study, we evaluated an extract of enzymatically hydrolyzed Citrus unshiu peel (εCUP) for anti-cancer effects in human pancreatic cancer. Treatment with εCUP suppressed the growth and migration of human pancreatic cancer cells by maximally 50% and more than 30%, respectively, but treatment with εCUP did not suppress the growth and migration of human umbilical vein endothelial cells (HUVECs). Naringenin and hesperetin were newly generated by enzymatic hydrolysis, and they showed a unique potential to regulate mitogen-activated protein kinase and focal adhesion kinase. Treatment with narirutin- and hesperidin-deleted εCUP (Δnar./hes.) soothed the pro-angiogenic effect in HUVECs while retaining a strong anti-cancer effect in vitro and in vivo, suggesting that Δnar./hes. might be an effective reagent to improve conditions of pancreatic cancer patients with innoxiousness.