Effects of cyclopentenone prostaglandins on the expression of heme oxygenase-1 in MCF-7 cells

Abstract

Cyclopentenone prostaglandins (cyPGs) are produced by dehydration of precursor molecules. The cyPGs are reported to have proapoptotic effects in a variety of cell types. However, cyPGs, particularly 15-deoxy-Delta(12,14)- prostaglandin J(2) (15d-PGJ(2)), can also exert cytoprotective effects at relatively low concentrations. The cytoprotective activity of cyPGs appears to be mediated by the reactive alpha,beta-unsaturated carbonyl group located in the cyclopentene ring. In this study, we investigated the effect of cyPGs on the expression of heme oxygenase-1 (HO-1), a ubiquitous stress-responsive enzyme that catalyzes oxidative cleavage of heme to form iron, carbon monoxide, and biliverdin. Treatment of the human breast cancer cell line (MCF-7) with 15d-PGJ(2) resulted in a concentration- and time-dependent increase in the expression of HO-1, whereas prostaglandin A(2) (PGA(2)) and the non-PG derivative 2-cyclopenten-1-one failed to induce HO-1 expression at the protein level. RT-PCR revealed that the expression of HO-1 mRNA was induced at 6 h by 15d-PGJ(2) at 10 mu M. However, PGA(2) induced HO-1 mRNA expression at a higher concentration (30 mu M). 2-Cyclopenten-1-one did not induce the expression of HO-1 mRNA at all. Likewise, 15d-PGJ(2) treatment for 6 h led to phosphorylation of Akt/protein kinase B (PKB) to a greater extent than that achieved with PGA(2). Thus, the induction of HO-1 expression and the activation of Akt/PKB by 15d-PGJ(2) and PGA(2) are likely to confer cytoprotective or antiapoptotic effects exerted by these cyPGs.