title: Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling.
abstract: Osteosarcoma (OS) is the most common non-hematologic primary malignancy of bone, and multiple chemotherapeutic agents have been applied in the treatment of OS for over 40 years. Nevertheless, due to the poor prognosis of OS, it is essential to develop a novel treatment strategy. Evodiamine (EVO), a quinolone alkaloid extracted from the fruit of Evodia rutaecarpa, has been demonstrated to inhibit tumor cell proliferation. Thus, the main aim of the present study was to investigate the anti-proliferative and apoptosis-inducing effects of evodiamine (EVO) on human OS 143B cells, but also the possible mechanisms underlying these effects. The results of crystal violet staining, flow cytometry, western blot analysis and an in vivo experiment demonstrated that EVO exhibits significant inhibitory effects on cell proliferation, exhibits apoptosis-inducing effects and arrests the cell cycle in 143B cells. According to our findings of polymerase chain reaction (PCR), western blot analysis and recombinant adenoviral transfection, we confirmed that EVO upregulates both the protein and gene levels of phosphatase and tensin homolog (PTEN) in a concentration-dependent manner in 143B cells. Overexpression of PTEN reinforced the anti-proliferative effect of EVO in the 143B cells, while knockdown of PTEN upregulated PI3K/Akt signaling transduction and reversed the inhibitory effect of EVO on 143B cell proliferation. Further analysis indicated that EVO upregulated the expression of PTEN by inactivating PI3K/Akt signaling by decreasing phosphorylated Akt1/2. Based on the above results, we conclude that PTEN/PI3K/Akt signaling is involved in the inhibitory effect on human OS 143B cell proliferation by EVO.
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Meng
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Ke-Jie
authors.initials: KJ
authors.lastname: Shu
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Ran-Xi
authors.initials: RX
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Pi
authors.affiliation: Pharmacy School of Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Ke
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Deng
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011799:Quinazolines / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011799:Quinazolines; C049639:evodiamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt