title: Embelin inhibits growth and induces apoptosis through the suppression of Akt/mTOR/S6K1 signaling cascades.
abstract: BACKGROUND
  Akt/mTOR/S6K1 signaling cascades play an important role both in the survival and proliferation of tumor cells.
  
  
  METHODS
  In the present study, we investigated the effects of embelin (EB), identified primarily from the Embelia ribes plant, on the Akt/mTOR/S6K1 activation, associated gene products, cellular proliferation, and apoptosis in human prostate cancer cells.
  
  
  RESULTS
  EB exerted significant cytotoxic and suppressive effects on Akt and mTOR activation against androgen-independent PC-3 cells as compared to androgen-dependent LNCaP cells. Moreover, EB suppressed the constitutive activation of Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, down-regulation of anti-apoptotic (Bcl-2, Bcl-xL, survivin, IAP-1, and IAP-2) and proliferative (cyclin D1) proteins, activation of caspase-3, and cleavage of PARP. We also observed that EB can significantly enhance the apoptotic effects of a specific pharmacological Akt inhibitor when used in combination and also caused broad inhibition of all the three kinases in Akt/mTOR/S6K1 signaling axis in PC-3 cells.
  
  
  CONCLUSIONS
  EB inhibits multiple signaling cascades involved in tumorigenesis and can be used as a potential therapeutic candidate for both the prevention and treatment of prostate cancer.
authors.affiliation: College of Oriental Medicine and Institute of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Seong Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Sung-Moo
authors.initials: SM
authors.lastname: Kim
authors.forename: Hang
authors.initials: H
authors.lastname: Bae
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Nam
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Seok-Geun
authors.initials: SG
authors.lastname: Lee
authors.forename: Bum Sang
authors.initials: BS
authors.lastname: Shim
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyoo Seok
authors.initials: KS
authors.lastname: Ahn
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Choi
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D000728:Androgens / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000728:Androgens; D016227:Benzoquinones; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; C010945:embelin