title: Tetrandrine inhibits the proliferation of human osteosarcoma cells by upregulating the PTEN pathway.
abstract: Tetrandrine (TET) is a natural product isolated from the Chinese herb Stephania tetrandra S. Moore and has been reported to have antiproliferation and apoptosis-inducing activity in various malignant tumor cells. However, the exact molecular mechanisms underlying these effects remain unclear. In the present study, we tested the antiproliferation effect of TET on osteosarcoma (OS) 143B cells and explored the possible potential molecular mechanism in this process. Using CCK-8 assay and flow cytometry, we found that TET inhibited proliferation, induced apoptosis and arrested the cell cycle of the 143B cells. Using a xenograft tumor model of human OS, tetrandrine was found to inhibit tumor growth in vivo. TET increased the protein level of phosphatase and tensin homolog (PTEN) and decreased its phosphorylation as detected by western blot analysis and immunohistochemistry.Overexpression of PTEN strengthened the anticancer effect of TET, while knockdown of PTEN attenuated it. Meanwhile, TET activated p38 MAPK and increased its phosphorylation. Our findings suggest that TET may be a potential anticancer drug for OS. In addition, its effects may be mediated by the upregulation of PTEN. Moreover the expression alteration of PTEN and p-PTEN was mediated by the TET-induced activation of p38 MAPK in a direct or indirect manner.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Tian
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Ran-Xi
authors.initials: RX
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Shuai-Hong
authors.initials: SH
authors.lastname: Luo
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Hou-Qing
authors.initials: HQ
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Yuzhong, Chongqing 400010, P.R. China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Deng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000008:administration & dosage* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; C009438:tetrandrine; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human