title: Cyproheptadine-induced myeloma cell apoptosis is associated with inhibition of the PI3K/AKT signaling.
abstract: Recent studies revealed that the anti-allergic cyproheptadine displays anti-blood cancer activity. However, its mechanism is still elusive. In this study, cyproheptadine was found to decrease the expression of anti-apoptotic proteins, including Bcl-2, Mcl-1, and XIAP. More importantly, cyproheptadine-induced apoptosis was accompanied by suppressing AKT activation in myeloma cells. In the subsequent study, cyproheptadine was found to inhibit insulin-like growth factor 1-triggered AKT activation in a time- and concentration-dependent manner. Specifically, cyproheptadine blocked AKT translocation from nuclei for phosphorylation. This inhibition led to suppressed activation of p70S6K and 4EBP1, two key downstream signaling proteins in the PI3K/AKT pathway. However, cyproheptadine did not display inhibition on activation of IGF-1R or STAT3, possible upstream signals of AKT activation. These results further demonstrated that cyproheptadine suppresses the PI3K/AKT signaling pathway, which is probably critical for cyproheptadine-induced MM cell apoptosis.
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Biyin
authors.initials: B
authors.lastname: Cao
authors.forename: Shunye
authors.initials: S
authors.lastname: Zhou
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zhu
authors.forename: Zubin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tingjun
authors.initials: T
authors.lastname: Hou
authors.forename: Xinliang
authors.initials: X
authors.lastname: Mao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D003533:Cyproheptadine / Q000494:pharmacology*; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003533:Cyproheptadine; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C087000:EIF4EBP1 protein, human
keywords: PI3K/AKT signaling pathway; cyproheptadine; multiple myeloma