Investigation of the effect of UII/UTR pathway on cell death in A549 cell line

UII has neurohormone-like activity. The UII/UTR pathway mainly stimulates the RhoA/ROCK, MAPKs and PI3K/AKT pathways and stimulates cardiac fibrosis, tumor growth and cell proliferation via these pathways. SB657510, a UII/UTR pathway antagonist, blocks tumor growth. The fact that the UII/UTR pathway activates the NFκB and MAPK pathways and its antagonist blocks tumor growth suggests that this pathway may also be associated with apoptosis. There are no studies directly investigating the relationship of the UII/UTR pathway with apoptosis. Therefore, in our study, we investigated the effect of the UII/UTR pathway on apoptosis using the A549 cell line. The A549 cell line is stimulated with the UT/UTR pathway agonist UII and its antagonist SB657510.We determined that UII does not affect A549 cell viability, but SB657510 reduces cell viability by MTT assay. mRNA expression of CASP3, CASP8 and CASP9 does not change upon UII stimulation. The anti-apoptotic gene BCL2 mRNA expression increases, but the increase is not statistically significant. mRNA expression of CASP3, CASP8 and CASP9 increases upon SB657510 stimulation. It is found that SB657510 increased the number of apoptotic cells more than UII by flow cytometry assay. Our study shows that UII does not change cell viability and caspase expression, however UII antagonist both decreases cell viability and increases gene expression of caspases involved in apoptosis. Our data show that the UII pathway is associated with apoptosis. Therefore, it points out that the UII/UTR pathway might be an alternative pathway for new therapies that can be used in lung cancer in relation to apoptosis. Key words: UT/UTR pathway, UII, SB657510, Apoptosis, A549