title: ECPIRM, a Potential Therapeutic Agent for Cutaneous T-Cell Lymphoma, Inhibits Cell Proliferation and Promotes Apoptosis via a JAK/STAT Pathway.
abstract: Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells.
  
  
  
  The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM.
  
  
  
  The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis.
  
  
  
  ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling.
  
  
  
  ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Ma
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Mengli
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Qian
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015474:Isotretinoin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C000608162:N-(4-ethoxycarbonylphenyl)isoretinamide; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D015474:Isotretinoin
keywords: Cutaneous T-cell lymphomas; ECPIRM; JAK/STAT pathway; RAR; RXR; Retinoids.