title: Polysaccharopeptide enhanced the anti-cancer effect of gamma-tocotrienol through activation of AMPK.
abstract: BACKGROUND
  Prostate cancer (PCa) frequently relapses after hormone ablation therapy. Unfortunately, once progressed to the castration resistant stage, the disease is regarded as incurable as prostate cancer cells are highly resistant to conventional chemotherapy.
  
  
  METHODS
  We recently reported that the two natural compounds polysaccharopeptide (PSP) and Gamma-tocotrienols (γ-T3) possessed potent anti-cancer activities through targeting of CSCs. In the present study, using both prostate cancer cell line and xenograft models, we seek to investigate the therapeutic potential of combining γ-T3 and PSP in the treatment of prostate cancer.
  
  
  RESULTS
  We showed that in the presence of PSP, γ-T3 treatment induce a drastic activation of AMP-activated protein kinase (AMPK). This was accompanied with inactivation of acetyl-CoA carboxylase (ACC), as evidenced by the increased phosphorylation levels at Ser 79. In addition, PSP treatment also sensitized cancer cells toward γ-T3-induced cytotoxicity. Furthermore, we demonstrated for the first time that combination of PSP and γ-T3 treaments significantly reduced the growth of prostate tumor in vivo.
  
  
  CONCLUSIONS
  Our results indicate that PSP and γ-T3 treaments may have synergistic anti-cancer effect in vitro and in vivo, which warrants further investigation as a potential combination therapy for the treatment of cancer.
authors.forename: Ji
authors.initials: J
authors.lastname: Liu
authors.forename: Eunice Yuen-Ting
authors.initials: EY
authors.lastname: Lau
authors.forename: Jiezhong
authors.initials: J
authors.lastname: Chen
authors.forename: Joan
authors.initials: J
authors.lastname: Yong
authors.forename: Kai Dun
authors.initials: KD
authors.lastname: Tang
authors.forename: Jessica
authors.initials: J
authors.lastname: Lo
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology, Qld, Australia. tkwlee@hku.hk.
authors.forename: Terence Kin-Wah
authors.initials: TK
authors.lastname: Lee
authors.forename: Ming-Tat
authors.initials: MT
authors.lastname: Ling
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002460:Cell Line; D002839:Chromans / Q000008:administration & dosage*; D004357:Drug Synergism; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D011509:Proteoglycans / Q000008:administration & dosage*; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D011509:Proteoglycans; C093216:polysaccharide peptide; D014810:Vitamin E; C013649:plastochromanol 8; D055372:AMP-Activated Protein Kinases