Abstract
Colorectal cancer is one of the leading causes of cancer deaths worldwide. Currently, chemotherapy is the primary way for colorectal cancer, but with severe side effects. Therefore, it is urgent to find safer and more effective adjuvant treatment methods. At present, natural active substances are promising alternatives, as numerous studies have demonstrated possible synergistic anticancer effects in plant-active polyphenols. In the present study, the combined effect of procyanidins (PC) (from peanut skin) and resveratrol (RES) (from peanut buds) on the synergistic anticancer potential was investigated. CACO-2 and HCT-8 cells were served as colorectal cancer models, and HEPG-2 and HUH-7 cells were served as liver cancer models to observe the effects of PC and RES alone or in combination on the growth and proliferation of these four types of cancer cells. The results revealed that both PC and RES could inhibit the cells' proliferation in a manner with concentration-dependent, but they exerted synergistic anticancer effects only on CACO-2 cells. PC and RES could synergistically inhibit CACO-2 cell clone formation, inducing apoptosis of CACO-2 cells and blocking their cell cycle in G0/G1 phase. Additionally, as observed by the results of Western blot assay, the combined effect of PC and RES also inhibited the phosphorylation of Thr308, Ser473, and ERK and promoted the phosphorylation of IKBα and NF-κB in CACO-2 cells. These findings collectively indicate that PC combined with RES might exert synergistic anticancer effects by regulating AKT, ERK, and NF-κB signaling pathways.