Anti-cancer effects of the aqueous extract of Orostachys japonica A. Berger on 5-fluorouracil-resistant colorectal cancer via MAPK signalling pathways in vitro and in vivo

Orostachys japonica A. Berger, also known as Wa-song in Korea, has traditionally been used as a folk medicine, but the potential anti-cancer effects of aqueous extract of Orostachys japonica (OJe) have not yet been thoroughly investigated.To evaluate the anti-cancer effects of OJe, its possible mechanisms of action were investigated in 5-fluorouracil (5-FU) resistant SNU-C5/5-FUR colorectal cancer cells.The functional compounds of OJe were identified with high performance liquid chromatography. The anti-cancer effects of OJe in SNU-C5/5-FUR cells were investigated by a cell viability assays, flow cytometry analysis, and a subcutaneous xenograft model employing BALB/c-nude mice. Possible signalling pathways were assayed with Western blotting.OJe (250 μg/ml) showed anti-cancer effects in SNU-C5/5-FUR cells, that were mediated via apoptosis as well as cell cycle arrest at the G0/G1 phase. Gallic acid and (-)-epicatechin, the major functional components of OJe, induced cell cycle arrest. OJe treatment (250 mg/kg, p.o.) produced a significant anti-proliferative effect in the xenograft model via decreased β-catenin/GSK3β and increased p27 expression. OJe treatment significantly activated ERK and p38 both in vitro and in vivo.These results suggest that OJe has anti-proliferative effects on 5-FU-resistant colorectal cancer cells via regulation of MAPK signalling pathways.