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Cyproheptadine‐induced myeloma cell apoptosis is associated with inhibition of the PI 3K/ AKT signaling
Author(s) -
Li Jie,
Cao Biyin,
Zhou Shunye,
Zhu Jingyu,
Zhang Zubin,
Hou Tingjun,
Mao Xinliang
Publication year - 2013
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12193
Subject(s) - cyproheptadine , protein kinase b , pi3k/akt/mtor pathway , xiap , apoptosis , phosphorylation , chemistry , signal transduction , microbiology and biotechnology , cancer research , biology , programmed cell death , biochemistry , caspase , receptor , serotonin
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 4 EBP 1, two key downstream signaling proteins in the PI 3K/ AKT pathway. However, cyproheptadine did not display inhibition on activation of IGF ‐1R or STAT 3, possible upstream signals of AKT activation. These results further demonstrated that cyproheptadine suppresses the PI 3K/ AKT signaling pathway, which is probably critical for cyproheptadine‐induced MM cell apoptosis.