Piperlongumine induces apoptosis and reduces bortezomib resistance by inhibiting STAT3 in multiple myeloma cells
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Yao Yao1,2,4,*, Yueyue Sun1,2,4,*, Min Shi1,2,4,*, Dandan Xia1,2,4, Kai Zhao1,2,4, Lingyu Zeng1,2,4, Ruosi Yao1,2,4, Ying Zhang3, Zhenyu Li2, Mingshan Niu1,2,4, Kailin Xu1,2,4
1Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China
2Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China
3Laboratory of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu, China
4Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China
*These authors have contributed equally to this work
Mingshan Niu, email: [email protected]
Keywords: multiple myeloma, STAT3, piperlongumine, bortezomib resistance, immunoproteasome
Received: September 17, 2015 Accepted: September 02, 2016 Published: September 13, 2016
Effective new therapies are urgently needed for the treatment of multiple myeloma (MM), an incurable hematological malignancy. In this study, we evaluated the effects of piperlongumine on MM cell proliferation both in vivo and in vitro. Piperlongumine inhibited the proliferation of MM cells by inducing cell apoptosis and blocking osteoclastogenesis. Notably, piperlongumine also reduced bortezomib resistance in MM cells. In a disseminated MM mouse model, piperlongumine prolonged the survival of tumor-bearing mice without causing any obvious toxicity. Mechanistically, piperlongumine inhibited the STAT3 signal pathway in MM cells by binding directly to the STAT3 Cys712 residue. These findings suggest that the clinical use of piperlongumine to overcome bortezomib resistance in MM should be evaluated.
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