Down-regulation of Akt by methanol extracts of Impatiens balsamina L. promotes apoptosis in human oral squamous cell carcinoma cell lines

J Oral Pathol Med. 2015 Jul;44(6):420-8. doi: 10.1111/jop.12248. Epub 2014 Sep 12.

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.

Keywords: Akt; Bax; Impatiens balsamina L; oral squamous cell carcinoma; survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Chromones / pharmacology
  • Down-Regulation / drug effects*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / pathology
  • Humans
  • Imidazoles / pharmacology
  • Impatiens / chemistry*
  • Methanol / chemistry
  • Molar, Third / cytology
  • Morpholines / pharmacology
  • Mouth Mucosa / cytology
  • Mouth Mucosa / drug effects
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / enzymology
  • Mouth Neoplasms / pathology
  • Naphthoquinones / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Antineoplastic Agents, Phytogenic
  • Chromones
  • Imidazoles
  • Morpholines
  • Naphthoquinones
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts
  • Protein Kinase Inhibitors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • sepantronium
  • Methanol