title: Salidroside induces apoptosis and autophagy in human colorectal cancer cells through inhibition of PI3K/Akt/mTOR pathway.
abstract: The role of salidroside in colon cancer remains unknown. Here we show that salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea, exhibited potent anti-proliferative properties in human colorectal cancer cells via inducing apoptosis and autophagy. We ascertained that salidroside exerts an inhibitory effect on the proliferation of human colorectal cancer cells in a dose-dependent manner. In addition, salidroside induced cell apoptosis, accompanied by an increase of chromatin condensation and nuclear fragmentation, and a decrease of Bcl-2/Bax protein expression ratio. We also found that salidroside induced autophagy, evidenced by increased LC3+ autophagic vacuoles, positive acridine orange-stained cells, enhanced conversion of LC3-I to LC3-II, and elevation of Beclin-1. Treatment with autophagy-specific inhibitors [3-methyladenine (3-MA) and bafilomycin A1 (BA)] enhanced salidroside-induced apoptosis, indicating that salidroside-mediated autophagy may protect HT29 cells from undergoing apoptotic cell death. Additionally, salidroside decreased the phosphorylation of PI3K, Akt and mTOR. Treatment with PI3K inhibitor LY294002 augmented the effects of salidroside on the expression of Akt and mTOR. These findings indicate that salidroside could suppress the PI3K/Akt/mTOR signaling pathways. This study may provide a rationale for future clinical application using salidroside as a chemotherapeutic agent for human colorectal cancer.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Fan
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology; D004354:Drug Screening Assays, Antitumor; D005960:Glucosides / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000071186:Beclin-1; D005960:Glucosides; D008869:Microtubule-Associated Proteins; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; C491997:BECN1 protein, human; C477012:MAP1LC3A protein, human; C546842:MTOR protein, human; C009172:rhodioloside