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KMID : 0624620150480100571
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BMB Reports
2015 Volume.48 No. 10 p.571 ~ p.576
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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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Song In-Sung
Jeong Yu-Jeong
Nyamaa Bayalagmaa
Jeong Seung-Hun
Kim Hyoung-Kyu
Kim Na-Ri
Ko Kyung-Soo
Rhee Byoung-Doo
Han Jin
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Abstract
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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 NF-κB signaling pathway, but does not cause cell cycle arrest in KMS20 MM cells. SB743921-mediated inhibition of the NF-κB 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.
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KEYWORD
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SB743921, NF-κB, multiple myeloma, combination therapy, superoxide dismutase 2, Mcl-1
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