Please use this identifier to cite or link to this item: https://doi.org/10.3389/fphar.2018.00531
Title: Anti-myeloma effects of icariin are mediated through the attenuation of JAK/STAT3-dependent signaling cascade
Authors: Jung Y.Y.
Lee J.H.
Nam D.
Narula A.S.
Namjoshi O.A.
Blough B.E.
Um J.-Y.
Sethi G. 
Ahn K.S.
Keywords: Apoptosis; Icariin; JAKs; Multiple myeloma; STAT3
Issue Date: 2018
Publisher: Frontiers Media S.A.
Citation: Jung Y.Y., Lee J.H., Nam D., Narula A.S., Namjoshi O.A., Blough B.E., Um J.-Y., Sethi G., Ahn K.S. (2018). Anti-myeloma effects of icariin are mediated through the attenuation of JAK/STAT3-dependent signaling cascade. Frontiers in Pharmacology 9 (MAY) : 531. ScholarBank@NUS Repository. https://doi.org/10.3389/fphar.2018.00531
Abstract: Because of the essential role of signal transducer and activator of transcription 3 (STAT3) in proliferation, anti-apoptosis, and chemoresistance of multiple myeloma (MM), we investigated whether icariin, a prenylated flavonol glycoside, inhibits both constitutive and inducible STAT3 activation in human myeloma cell lines. We noted that icariin could block constitutive STAT3 phosphorylation as well as its nuclear translocation and DNA binding ability in U266 cells. Icariin also suppressed IL-6-induced STAT3 activation through the inhibition of upstream kinases (Janus activated kinase-1 and -2, and c-Src). We found that icariin downregulated the protein expression of STAT3 downstream target gene products such as Bcl-2, Bcl-xl, survivin, IAP-1/2, COX-2, VEGF, and matrix metallopeptidase 9 (MMP-9) in a concentration-dependent manner. Moreover, this flavonoid also exhibited the capacity to significantly induce apoptosis and suppress proliferation of MM cells. Interestingly, this agent also significantly potentiated the apoptotic effects of bortezomib through the suppression of STAT3 activation in MM cells. Altogether, our data indicates that the potential application of icariin as a STAT3 blocker in myeloma therapy. © 2018 Jung, Lee, Nam, Narula, Namjoshi, Blough, Um, Sethi and Ahn.
Source Title: Frontiers in Pharmacology
URI: http://scholarbank.nus.edu.sg/handle/10635/152590
ISSN: 16639812
DOI: 10.3389/fphar.2018.00531
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