title: Lycorine induces cell death in MM by suppressing Janus Kinase/signal transducer and activator of transcription via inducing the expression of SOCS1.
abstract: Despite the use of novel anti-myeloma agents,nearly all patients will eventually relapse or become refractory to drug treatment. New and more effective drugs for multiple myeloma (MM) are urgently needed. The JAK-STAT signaling pathway is important in the proliferation of myeloma cells.Lycorine,a natural alkaloid extracted from amaryllidaceae, has shown anti-tumor effects against a variety of solid tumors. However, its effects on MM remain unclear.In this study,we found that lycorine inhibited cellular viability and induced cell death in MM cell lines and primary myeloma cells which were derived from our four MM patients. The study showed that myeloma cells' cycle was being arrested under the G0/G1 phase followed by the lycorine treatment. Further mechanism analysis demonstrated that lycorine inhibited JAK2/STAT signaling through upregulation of SOCS1 in MM cells and patient MM cells.Importantly, we found that knockdown of HDAC8 resulted in increased expression of SOCS1. Collectively, our findings suggested lycorine acted as a potent novel histone deacetylase inhibitor and inhibited JAK2/STAT signaling through upregulation of SOCS1 in MM cells.
authors.affiliation: Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 XueYuan Western Road, Wenzhou 325027, China.
authors.forename: Zhouxiang
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University,NanBai Xiang, Wenzhou 325000, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University,NanBai Xiang, Wenzhou 325000, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University,NanBai Xiang, Wenzhou 325000, China.
authors.forename: Haige
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University,NanBai Xiang, Wenzhou 325000, China. Electronic address: jiangsongfu12@126.com.
authors.forename: Songfu
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University,NanBai Xiang, Wenzhou 325000, China. Electronic address: yukang1_2@126.com.
authors.forename: Kang
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University,NanBai Xiang, Wenzhou 325000, China. Electronic address: myy8635@126.com.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000368:Aged; D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D053612:Janus Kinases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000201:enzymology* / Q000473:pathology*; D010617:Phenanthridines / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D047151:Amaryllidaceae Alkaloids; D010617:Phenanthridines; D050796:STAT3 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases; D006655:Histone Deacetylases; C015330:lycorine
keywords: Histone deacetylase inhibitor; JAK/STAT; Lycorine; Multiple myeloma