title: Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor.
abstract: Emodin is an active component of a traditional Chinese and Japanese medicine isolated from the root and rhizomes of Rheum palmatum L. Here, we show that emodin significantly induces cytotoxicity in the human myeloma cells through the elimination of myeloid cell leukemia 1 (Mcl-1). Emodin inhibited interleukin-6-induced activation of Janus-activated kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3), followed by the decreased expression of Mcl-1. Activation of caspase-3 and caspase-9 was triggered by emodin, but the expression of other antiapoptotic Bcl-2 family members, except Mcl-1, did not change in the presence of emodin. To clarify the importance of Mcl-1 in emodin-induced apoptosis, the Mcl-1 expression vector was introduced into the human myeloma cells by electroporation. Induction of apoptosis by emodin was almost abrogated in Mcl-1-overexpressing myeloma cells as the same level as in parental cells, which were not treated with emodin. In conclusion, emodin inhibits interleukin-6-induced JAK2/STAT3 pathway selectively and induces apoptosis in myeloma cells via down-regulation of Mcl-1, which is a good target for treating myeloma. Taken together, our results show emodin as a new potent anticancer agent for the treatment of multiple myeloma patients.
authors.affiliation: Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawaku, Tokyo 142-8501, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Muto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hori
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Akari
authors.initials: A
authors.lastname: Saitoh
authors.forename: Iho
authors.initials: I
authors.lastname: Yasuda
authors.forename: Tadahito
authors.initials: T
authors.lastname: Maekawa
authors.forename: Tomoe
authors.initials: T
authors.lastname: Uchida
authors.forename: Keiko
authors.initials: K
authors.lastname: Asakura
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakazato
authors.forename: Toshio
authors.initials: T
authors.lastname: Kaneda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kizaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004642:Emodin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D015850:Interleukin-6; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053614:Janus Kinase 2; D020928:Mitogen-Activated Protein Kinases; D004642:Emodin