title: Autophagy induced by FTY720 promotes apoptosis in U266 cells.
abstract: Despite recent treatment advances, multiple myeloma (MM) remains incurable and patients develop a progressively relapsing disease with subsequent poor prognosis. Studies have shown FTY720 has activities against a number of hematological malignancies including MM, no reports about autophagy induced by FTY720 in MM. Therefore, we investigated the potential application of FTY720 on MM using U266 cell line. We observed that FTY720 could induce caspase-3 dependent apoptosis in a dose- and time-dependent manner in U266 cells. FTY720 caused apoptosis by down-regulating antiapoptotic proteins Mcl-1, bcl-2, survivin and cleavage of Bid. Interestingly, FTY720 induce autophagy which could promote the apoptosis in U266 cells. Furthermore, activation of reactive oxygen species (ROS) regulates FTY720 induced apoptosis and autophagy in U266 cells. The study implicated that FTY720 could be a good candidate for MM treatment.
authors.affiliation: Department of Hematology, Shengjing Hospital, China Medical University, 36 Sanhao Street, Heping District, 110004 Shenyang, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Liao
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Qihui
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Huihan
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Zhuogang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011409:Propylene Glycols / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077022:Survivin
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011409:Propylene Glycols; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D000077022:Survivin; D053148:Caspase 3; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine