Influence of prostaglandin A2 and 2-methoxyestradiol on mitogen-activated protein kinase (MAPK) expression levels in malignant cell lines

Mammalian cells often use the highly conserved mitogen-activated protein kinase (MAPK) or extracellular signal regulated protein kinase (ERK) cascades to transmit intracellular instructions. These signaling pathways have been proposed to regulate a diverse range of biological functions including apoptosis. Since 2-methoxyestradiol (2ME) and prostaglandin A(2) (PGA(2)) play an active role in the induction of apoptosis, the influence of 1 mu M 2ME or 20 mu g/ml PGA(2) was investigated on ERK1/2 expression levels in three cancer cell lines. PGA(2) exposure led to a statistically significant increase in ERK1/2 expression levels of HeLa and WHCO3 cells. In contrast to the HeLa and WHCO3 cancer cell lines, no effect on ERK1/2 expression levels was observed after exposure of PGA(2) to MCF-7 cells. 2ME caused a statistically significant increase in ERK1/2 expression levels in HeLa, MCF-7 and WHCO3 cells. WHCO3 cells were shown to be more susceptible to the effects of PGA(2) and 2ME compared to the other two cancer cell lines. Since the characteristics of both PGA(2) and 2ME render them as possible anti-tumor agents when compared to conventional chemotherapeutic treatments, understanding the functional role of signaling events and their regulation by interfering pathways after exposure of cells to PGA(2) and 2ME respectively, will provide new insights into mechanisms involved in malignant cell proliferation.