title: Piperlongumine induces apoptosis and reduces bortezomib resistance by inhibiting STAT3 in multiple myeloma cells.
abstract: 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.
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Xia
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Ruosi
authors.initials: R
authors.lastname: Yao
authors.affiliation: Laboratory of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Mingshan
authors.initials: M
authors.lastname: Niu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China.|Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.|Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000069286:Bortezomib / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004148:Dioxolanes / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism; D010881:Piperidones
chemical_list: D000970:Antineoplastic Agents; D000069286:Bortezomib; D016207:Cytokines; D004148:Dioxolanes; D050796:STAT3 Transcription Factor; D019014:fas Receptor; C498077:piperlongumine; D010881:Piperidones
keywords: STAT3; bortezomib resistance; immunoproteasome; multiple myeloma; piperlongumine