Attenuation of STAT3 Signaling Cascade by Daidzin Can Enhance the Apoptotic Potential of Bortezomib against Multiple Myeloma

Daidzin (DDZ) extracted from (Fabaceae) is a widely known phytoestrogen. DDZ can display anti-cancer activities against breast and prostate cancers, but its anti-oncogenic actions in multiple myeloma (MM) cells have not been studied. The signal transducer and activator of transcription 3 (STAT3) can...

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Published inBiomolecules (Basel, Switzerland) Vol. 10; no. 1; p. 23
Main Authors Yang, Min Hee, Jung, Sang Hoon, Chinnathambi, Arunachalam, Alahmadi, Tahani Awad, Alharbi, Sulaiman Ali, Sethi, Gautam, Ahn, Kwang Seok
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 23.12.2019
MDPI
Subjects
Antibodies
Apoptosis
Bortezomib
Breast cancer
Cancer therapies
Cell cycle
Cell differentiation
Cell proliferation
daidzin
Dehydrogenases
Janus kinase
Kinases
Multiple myeloma
Pervanadate
Phosphatase
Phosphorylation
Polymerase chain reaction
Prostate cancer
Protein-tyrosine-phosphatase
Proteins
Pueraria lobata
Src protein
stat3
Stat3 protein
Targeted cancer therapy
Transcription
United States > US
Japan
multiple myeloma
daidzin
bortezomib
STAT3
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Summary:Daidzin (DDZ) extracted from (Fabaceae) is a widely known phytoestrogen. DDZ can display anti-cancer activities against breast and prostate cancers, but its anti-oncogenic actions in multiple myeloma (MM) cells have not been studied. The signal transducer and activator of transcription 3 (STAT3) can control key processes including proliferation, differentiation, and survival in MM cells. Here, we noted that DDZ abrogated STAT3 activation (both constitutive as well as inducible) at Tyr705 and Ser727 in MM cells. Additionally, DDZ mitigated the phosphorylation of STAT3 upstream Janus-activated kinases (JAK1/2) and c-Src kinases. Pervanadate (tyrosine phosphatase blocker) exposure altered the DDZ-induced inhibition of STAT3 activation, thus affecting the action of this phytoestrogen on apoptosis. Moreover, DDZ impeded proliferation and augmented the apoptotic effects of bortezomib (Bor) in MM cells. Overall, the data indicate that DDZ may act as a potent suppressor of STAT3 signaling cascade, and the co-treatment of DDZ and Bor could be a promising therapeutic strategy, specifically in MM.
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These authors contributed equally to this study.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom10010023