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KSP inhibitor SB743921 induces death of multiple myeloma cells via inhibition of the NF-κB signaling pathway
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  • Journal title : BMB Reports
  • Volume 48, Issue 10,  2015, pp.571-576
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.10.015
 Title & Authors
KSP inhibitor SB743921 induces death of multiple myeloma cells via inhibition of the NF-κB signaling pathway
Song, In-Sung; Jeong, Yu Jeong; Nyamaa, Bayalagmaa; Jeong, Seung Hun; Kim, Hyoung Kyu; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin;
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 Abstract
SB743921 is a potent inhibitor of the spindle protein kinesin and is being investigated in ongoing clinical trials for the treatment of myeloma. However, little is known about the molecular events underlying the induction of cell death in multiple myeloma (MM) by SB743921, alone or in combination treatment. Here, we report that SB743921 induces mitochondria-mediated cell death via inhibition of the signaling pathway, but does not cause cell cycle arrest in KMS20 MM cells. SB743921-mediated inhibition of the pathway results in reduced expression of SOD2 and Mcl-1, leading to mitochondrial dysfunction. We also found that combination treatment with SB743921 and bortezomib induces death in bortezomib-resistant KMS20 cells. Altogether, these data suggest that treatment with SB743921 alone or in combination with bortezomib offers excellent translational potential and promises to be a novel MM therapy.
 Keywords
SB743921;;multiple myeloma;combination therapy;superoxide dismutase 2;Mcl-1;
 Language
English
 Cited by
1.
KSP inhibitor SB743921 inhibits growth and induces apoptosis of breast cancer cells by regulating p53, Bcl-2, and DTL, Anti-Cancer Drugs, 2016, 27, 9, 863  crossref(new windwow)
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