title: Down-regulation of Akt by methanol extracts of Impatiens balsamina L. promotes apoptosis in human oral squamous cell carcinoma cell lines.
abstract: BACKGROUND
  The apoptotic activity of methanol extracts of Impatiens balsamina L. (MEIB) and related mechanisms in human oral squamous cell carcinoma (OSCC) cells have been systematically investigated.
  
  
  METHODS
  The effects of MEIB on human OSCC cell lines were investigated using trypan blue exclusion assay, MTS assay, Western blot, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead assay, Immunohistochemistry, reverse transcription-polymerase chain reaction, and promoter assay.
  
  
  RESULTS
  MEIB decreased cell viability and induced apoptosis in HSC-4 cells. Higher levels of p-Akt expression were observed in OSCC than in normal oral mucosa (NOM), and it correlated with poor survival of the patients. MEIB dephosphorylated p-Akt and decreased Akt expression through proteasome-dependent degradation. LY294002 (PI3K inhibitor) decreased p-Akt and Akt, resulting in enhancing MEIB-induced apoptosis. MEIB down-regulated the expression level of survivin protein at the transcriptional level and YM155 (survivin inhibitor) decreased survivin, which facilitated MEIB-induced apoptosis. MEIB and LY294002 significantly increased Bax, thereby inducing the conformational change, mitochondrial translocation, and oligomerization. In addition, MEIB-induced growth inhibition and apoptosis in OSC-20, another human OSCC cells were mediated by regulating Akt and it downstream targets, survivin and Bax.
  
  
  CONCLUSIONS
  These results suggest that MEIB may serve as a potential drug candidate for the treatment of human OSCC.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Shin
authors.affiliation: Department of Oral Pathology, School of Dentistry, Yangsan Campus of Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan, Korea.
authors.forename: Mi Heon
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Food Science and Nutrition, College of Health Welfare and Education, Gwangju University, Gwangju, Korea.
authors.forename: Ki-Han
authors.initials: KH
authors.lastname: Kwon
authors.affiliation: Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju, Korea.
authors.forename: BuYoung
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Biodegradable Material, Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D029069:Impatiens / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D008964:Molar, Third / Q000166:cytology; D009025:Morpholines / Q000494:pharmacology; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009285:Naphthoquinones / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002867:Chromones; D007093:Imidazoles; D000432:Methanol; D009025:Morpholines; D009285:Naphthoquinones; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C523798:sepantronium
keywords: Akt; Bax; Impatiens balsamina L; oral squamous cell carcinoma; survivin