title: Cytotoxic effects of escin on human castration-resistant prostate cancer cells through the induction of apoptosis and G2/M cell cycle arrest.
abstract: OBJECTIVE
  To evaluate the in vitro and in vivo effects of escin on human castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145.
  
  
  METHODS
  The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo efficacy of escin in CRPC cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice.
  
  
  RESULTS
  The treatment with escin significantly reduced cell viability of CRPC cells in a dose- and time-dependent manner. Escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with the concomitant induction of p21. In addition, escin significantly inhibited the growth of CRPC cells in xenograft models.
  
  
  CONCLUSIONS
  The results show that escin induced cytotoxic effects on CRPC cells through the induction of apoptosis and G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC.
authors.affiliation: Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Urology, Yanbian University Hospital, Yanji, Jilin Province, China.
authors.forename: Songzhe
authors.initials: S
authors.lastname: Piao
authors.affiliation: Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Minyong
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Urology, Konkuk University Hospital, Seoul, Republic of Korea.
authors.forename: Woo Suk
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yang-Sook
authors.initials: YS
authors.lastname: Chun
authors.affiliation: Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Kwak
authors.affiliation: Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: hhkim@snu.ac.kr.
authors.forename: Hyeon Hoe
authors.initials: HH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004928:Escin / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D064129:Prostatic Neoplasms, Castration-Resistant / Q000473:pathology*
chemical_list: D004928:Escin