Earticle

초록

영어

Background: Multiple myeloma (MM) is the second most prevalent hematologic malignancy and it is uniformly fatal. Although survival rate has been increased over the last few decades, MM remains as a largely incurable disease with mortality rate. A second generation of kinesin spindle protein (KSP) inhibitor is a new anti-cancer treatment and its targets the mitotic motor kinesin. Methods: MM cell line-KMS20 exhibited cell death, cell cycle arrest and mitochondrial Ca2+ concentrations, mitochondrial ROS level, mitochondrial membrane potential (ψΔm), oxygen consumption and ATP production, under non-treated and SB743921 treated conditions. Results: 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. Moreover, we found that combination treatment with SB743921 and bortezomib induces death in bortezomib- resistant KMS20 cells. Conclusion: Taken together, 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.

목차

ABSTRACT
 INTRODUCTION
 RESULTS
 DISCUSSION
 MATERIALS AND METHODS
 Acknowledgements
 REFERENCES

저자

• Bayalagmaa Nyamaa [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• In-Sung Song [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• Yu Jeong Jeong [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• Seung Hun Jeong [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• Hyoung Kyu Kim [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• Nari Kim [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• Kyung Soo Ko [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• Byoung Doo Rhee [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]
• Jin Han [ National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea ]

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