title: Celastrus orbiculatusextract triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in human colorectal cancer cells.
abstract: Celastrus orbiculatusis used as a folk medicine in China for the treatment of numerous diseases. The ethyl acetate extract ofCelastrus orbiculatus(COE) also displays a wide range of anti-cancer activities in the laboratory. However, the effectiveness of COE-induced autophagy and its mechanism of action in colorectal cancer cells have not been investigated thus far. The present study analyzed the effect of COE on HT-29 cell viability, apoptosis and autophagy using MTT assay, flow cytometry, transmission electron microscopy and western blotting. Additionally, the autophagy inhibitor 3-methyladenine and the autophagy inducer rapamycin were used to further explore the effects of COE-induced autophagy in HT-29 cells. The present study also examined whether the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway was involved in the regulation of COE-induced autophagy. The results revealed that COE inhibited HT-29 cell proliferation and decreased cell survival in a time- and dose-dependent manner, and that COE possessed the ability to induce both apoptosis and autophagy in HT-29 cells. Furthermore, autophagy and apoptosis induced by COE synergized to inhibit colorectal cancer growth. In addition, COE treatment decreased the phosphorylation of Akt and its downstream effectors mTOR and p70S6K. Taken together, these results demonstrate that both autophagy and apoptosis were activated during COE treatment of HT-29 cells, and that COE-induced autophagy decreases the viability of HT-29 cells via a mechanism that may depend on the PI3K/Akt/mTOR/p70S6K signaling pathway. Furthermore, compounds that induce autophagy administered in combination with COE may be an attractive strategy for enhancing the anti-tumor potency of COE in colorectal cancer.
authors.affiliation: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Department of Gastroenterology, The First People's Hospital of Yangzhou, The Second Clinical School of Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Dai
authors.affiliation: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hisamitsu
keywords: Celastrus orbiculatus extract; apoptosis; autophagy