TITLE:
The Effect of Antineoplastons A10 and AS2-1 and Metabolites of Sodium Phenylbutyrate on Gene Expression in Glioblastoma Multiforme
AUTHORS:
Stanislaw R. Burzynski, Sonali S. Patil
KEYWORDS:
Glioblastoma, Antineoplastons, Phenylbutyrate, Gene Expression, Pathways, Cell Cycle
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.10,
September
4,
2014
ABSTRACT:
Antineoplastons are
peptide and amino acid derivatives that occur naturally in the human body. They
inhibit the growth of neoplastic cells without growth inhibition of normal
cells. Phenylacetylglutaminate (PG) is an active ingredient of antineoplastons
A10 and AS2-1 (ANP) and is also a metabolic by-product of phenylbutyrate (PB).
The formulation of antineoplaston AS2-1 is a 4:1 mixture of phenylacetate (PN)
and PG. Antineoplaston A10 is a 4:1 mixture of PG and isoPG. This study
investigates the molecular mechanism of action of PG and PN. The Human U87
glioblastoma (GBM) cell line was used as the model system in this study. A
total human gene array screen using the Affymetrix Human Genome plus 2.0
oligonucleotide arrays was performed using mRNA derived from U87 cells exposed
to PG and PN. Pathway analysis was performed to allow the visualization of
effect on metabolic pathways and gene interaction networks. Our preliminary
results indicate that PG and PN interrupt signal transduction in RAS/MAPK/ERK
and PI3K/AKT/PTEN pathways, interfere with cell cycle, decrease metabolism and
promote apoptosis in human U87 GBM cells. The effect on multiple cellular pathways
and targets, suggests that ANP and PB are promising candidates for clinical
studies in GBM.