title: Inhibition of AKT signaling by supercritical CO2 extract of mango ginger (Curcuma amada Roxb.) in human glioblastoma cells.
abstract: BACKGROUND
  Mango ginger (Curcuma amada Roxb.) is a less-investigated herb for anticancer properties than other related Curcuma species. AKT (a serine/threonine protein kinase B, originally identified as an oncogene in the transforming retrovirus AKT8) plays a central role in the development and promotion of cancer. In this investigation, we have analyzed the effect of supercritical CO2 extract of mango ginger (CA) on the genetic pathways associated with AKT signaling in human glioblastoma cells.
  
  
  METHODS
  The inhibitory effect of supercritical CO2 extract of mango ginger (Curcuma amada) on AKT signaling was investigated in U-87MG glioblastoma cells.
  
  
  RESULTS
  CA was highly cytotoxic to glioblastoma cell line (IC50=4.92±0.81 µg/mL) compared to mHypoE-N1 normal mouse hypothalamus cell line (IC50=40.57±0.06 µg/mL). CA inhibits AKT (protein Kinase B) and adenosine monophophate -activated protein kinase α (AMPKα) phosphorylation significantly in a dose-dependent manner. The cell migration which is necessary for invasion and metastasis was also inhibited by CA treatment, with about 43% reduction at 20 µg/mL concentration. Analysis of mRNA and protein expression of genes associated with apoptosis, cell proliferation and angiogenesis showed that CA modulates expression of genes associated with apoptosis (Bax, Bcl-2, Bcl-X, BNIP3, caspase-3, mutant p53 and p21), cell proliferation (Ki67) and angiogenesis vascular endothelial growth factor (VEGF). Additionally, heat shock protein 90 (HSP90) and AMPKα genes interacting with the AKT signaling pathway were also downregulated by CA treatment.
  
  
  CONCLUSIONS
  These results indicate the molecular targets and mechanisms underlying the anticancer effect of CA in human glioblastoma cells.
authors.forename: Cheppail
authors.initials: C
authors.lastname: Ramachandran
authors.forename: Gilda
authors.initials: G
authors.lastname: Portalatin
authors.forename: Karl-W
authors.initials: KW
authors.lastname: Quirin
authors.forename: Enrique
authors.initials: E
authors.lastname: Escalon
authors.forename: Ziad
authors.initials: Z
authors.lastname: Khatib
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Melnick
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D030024:Curcuma; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012333:RNA, Messenger; D051058:Oncogene Protein v-akt; D051057:Proto-Oncogene Proteins c-akt