title: A novel cinnamide YLT26 induces breast cancer cells apoptosis via ROS-mitochondrial apoptotic pathway in vitro and inhibits lung metastasis in vivo.
abstract: BACKGROUND
  Breast cancer is the leading cause of cancer death among women worldwide and metastasis is the major cause of treatment failure. Thus, new treatment options for breast cancer, especially, drugs which could prevent metastasis, are pressingly needed.
  
  
  METHODS
  In the present study, we designed and synthesized a novel cinnamide derivative, (E)-N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (YLT26), which displayed potent inhibitory effects on breast cancer cells. The cell viability, apoptosis-inducing effect and reactive oxygen species (ROS) production were examined in 4T1 cells following treatment with YLT26. Meanwhile, apoptosis-related proteins levels were determined by western blotting. Finally, we evaluated the effects of YLT26 on breast tumor growth, lung metastases in vivo and the infiltration of myeloid-derived suppressor cells (MDSCs) in lung tissue.
  
  
  RESULTS
  Our results showed that the proliferation inhibitory effects of YLT26 were correlated with its apoptosis-inducing effect. Exposure to YLT26 induced mitochondrial transmembrane potential (∆Ψm) change, activated caspase-9, and downregulated the Bcl-2 expression, as well as enhanced ROS accumulation in 4T1 cells. Moreover, YLT26 significantly inhibited tumor growth without obvious side effects in the 4T1 tumor-bearing mice model. Immunohistochemistry analyze revealed YLT26 also induced apoptosis in vivo. More importantly, YLT26 also significantly inhibited lung metastases, which may be associated with the reduction of MDSCs.
  
  
  CONCLUSIONS
  The present study suggested that YLT26 could inhibit breast cancer cells proliferation via ROS-mitochondrial apoptotic pathway, delay breast tumor progression, and suppress lung metastases by impacting on the immunologic microenvironment in vivo. © 2015 S. Karger AG, Basel.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.forename: Mengyao
authors.initials: M
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xia
authors.forename: Ningyu
authors.initials: N
authors.lastname: Wang
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Song
authors.forename: Fengtian
authors.initials: F
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Zhu
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yang
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Luoting
authors.initials: L
authors.lastname: Yu
mesh_terms: D000813:Anilides / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002934:Cinnamates / Q000008:administration & dosage*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000813:Anilides; D002934:Cinnamates; C000601500:N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-3-(3,4,5-trimethoxyphenyl)acrylamide; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species