title: Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy.
abstract: Recently, the interest in natural products for the treatment of cancer is increasing because they are the pre-screened candidates. In the present study, we demonstrate the therapeutic effect of celastrol, a triterpene extracted from the root bark of Chinese medicine on gastric cancer. The proliferation of AGS and YCC-2 cells were most sensitively decreased in six kinds of gastric cancer cell lines after the treatment with celastrol. Celastrol inhibited the cell migration and increased G1 arrest in cell-cycle populations in both cell lines. The treatment with celastrol significantly induced autophagy and apoptosis and increased the expression of autophagy and apoptosis-related proteins. We also found an increase in phosphorylated AMPK following a decrease in all phosphorylated forms of AKT, mTOR and S6K after the treatment with celastrol. Moreover, gastric tumor burdens were reduced in a dose-dependent manner by celastrol administration in a xenografted mice model. Taken together, celastrol distinctly inhibits the gastric cancer cell proliferation and induces autophagy and apoptosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752; Asia Pacific International School, Seoul 139-852, Korea.
authors.forename: Kenny Seung Bin
authors.initials: KS
authors.lastname: Jang
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul 120-752; Brain Korea 21 Plus Project for Medical Sciences, Severance Medical Research Institute, Seoul 120-752, Republic of Korea.
authors.forename: Hye Ji
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul 120-752; Brain Korea 21 Plus Project for Medical Sciences, Severance Medical Research Institute, Seoul 120-752, Republic of Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Jo
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Brain Korea 21 Plus Project for Medical Sciences, Severance Medical Research Institute, Seoul 120-752, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752; Brain Korea 21 Plus Project for Medical Sciences, Severance Medical Research Institute, Seoul 120-752, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Chun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053978:Pentacyclic Triterpenes; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014183:Transplantation, Heterologous; D014315:Triterpenes / Q000627:therapeutic use / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C050414:celastrol