The Synergistic Effect of Gw9508 and S14161 Small Molecules on Apoptotic Gene Expression and Viability on A549 Cell Line
Sima Orouei, Maliheh Entezari, Mehrdad Hashemi, Kiavash Hushmandi, Abolfazl Movafagh
916
ABSTRACT
Aim: The
aim of this project was to investigate the effect of GW9508 and S14161 small
molecules on their viability and expression of apoptotic genes in the A549 cell
line.
Methods:In
this experiment, the A549 cell line was first cultured in DMEM medium
containing 10% FBS and then treated with different concentrations of both
compounds. MTT assay was performed on days 1, 3, and 5 to determine IC50 and to
compare the viability of cells treated with different concentrations of GW9508
and S14161. The qRT-PCR assay was employed to investigate the effects of S14161
and GW9508 with IC50 concentration on apoptosis induction, expression of genes
including p53, Bax, Bad and Bcl2.Both small molecules induced apoptosis by
increasing apoptotic Bax, Bad and P53 gene expression and decreasing Bcl2 gene
expression.
Results:Comparison
between the effect of S14161 and GW9508 individually and simultaneously on cell
viability using MTT assay results and gene analysis showed that the combined
use of both compounds had a stronger effect on inducing cell death and
apoptotic gene expression in a dose- and time-dependent manner, the more time
passes the more lethal power it gains.
Conclusion:Two
small molecules of GW9508 and S14161 activate apoptotic gene expression and
inhibit the anti-apoptotic gene in two different and parallel pathways, thus
being able to act synergistically under concomitant use and have a stronger
lethal effect on lung cancer cells.
Keywords:
S14161, GW9508, Lung cancer, Apoptotic, Cell line
ABSTRACT
Aim: The
aim of this project was to investigate the effect of GW9508 and S14161 small
molecules on their viability and expression of apoptotic genes in the A549 cell
line.
Methods:In
this experiment, the A549 cell line was first cultured in DMEM medium
containing 10% FBS and then treated with different concentrations of both
compounds. MTT assay was performed on days 1, 3, and 5 to determine IC50 and to
compare the viability of cells treated with different concentrations of GW9508
and S14161. The qRT-PCR assay was employed to investigate the effects of S14161
and GW9508 with IC50 concentration on apoptosis induction, expression of genes
including p53, Bax, Bad and Bcl2.Both small molecules induced apoptosis by
increasing apoptotic Bax, Bad and P53 gene expression and decreasing Bcl2 gene
expression.
Results:Comparison
between the effect of S14161 and GW9508 individually and simultaneously on cell
viability using MTT assay results and gene analysis showed that the combined
use of both compounds had a stronger effect on inducing cell death and
apoptotic gene expression in a dose- and time-dependent manner, the more time
passes the more lethal power it gains.
Conclusion:Two
small molecules of GW9508 and S14161 activate apoptotic gene expression and
inhibit the anti-apoptotic gene in two different and parallel pathways, thus
being able to act synergistically under concomitant use and have a stronger
lethal effect on lung cancer cells.
Keywords:
S14161, GW9508, Lung cancer, Apoptotic, Cell line