Jung Woo Kim1, Sang Hee Kim2, Ramesh Mariappan3, Daeun Moon4, Jinu Kim5, Sang-Pil Yoon6. 1. KIM JUNG WOO R&D Laboratory, Namwon, Jeollabuk-do, 55790, Republic of Korea. 2. Division of Creative Food Science for Health, Korea Food Research Institute, Jeollabuk-do, 55365, Republic of Korea. 3. Department of Cellular & Molecular Medicine, College of Medicine, Chosun University, Gwangju, 61452, Republic of Korea. 4. Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Republic of Korea. 5. Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, 63243, Republic of Korea; Department of Anatomy, College of Medicine, Jeju National University, Jeju, 63243, Republic of Korea. 6. Department of Anatomy, College of Medicine, Jeju National University, Jeju, 63243, Republic of Korea. Electronic address: spyoon@jejunu.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggest that OJe has anti-proliferative effects on 5-FU-resistant colorectal cancer cells via regulation of MAPK signalling pathways.
ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggest that OJe has anti-proliferative effects on 5-FU-resistant colorectal cancer cells via regulation of MAPK signalling pathways.