Effects of 15-Deoxy-?12,14-prostaglandin J2 on the Expression of p53 in MCF-7 Cells
Cyclopentenone prostaglandins (cyPGs) exert diverse cellular functions, such as anti-inflammatory and cytoprotective effects, via multiple mechanisms. CyPGs, especially those of the A and J series, are characterized by the presence of a chemically reactive ?,?-unsaturated carbonyl group. 15-Deoxy-?12,14-prostaglandin J2 (15d-PGJ2), a representative cyPG of the J series, has been reported to directly inhibit the activity of redox-sensitive transcription factors, such as activator protein-1 and nuclear factor-?B. In the present study, we examined the effects of 15d-PGJ2 on activation of p53 tumor suppressor in human breast cancer (MCF-7) cells. MCF-7 cells treated with 15d-PGJ2 exhibited elevated p53 protein expression in time- and concentration-related manners, whereas prostaglandin A2 (PGA2) and the nonprostaglandin derivative 2-cyclopenten-1-one exerted an effect to a lesser extent than did 15d-PGJ2. In addition, MCF-7 cells exposed to 15d-PGJ2 significantly accumulated p53 in both cytosolic and nuclear fractions. Despite the elevated levels of p53, its DNA-binding activity was reduced in 15d-PGJ2-treated MCF-7 cells. Moreover, isolated MCF-7 nuclear extracts directly treated with 15d-PGJ2 exhibite diminished DNA-binding ability of p53, while the same concentration of PGA2 or 2-cyclopenten-1-one was much less inhibitory. Thus, the electrophilic carbon center located in the ?,?-unsaturated carbonyl moiety of the cyclopentenone ring might be critical for the control of DNA-binding activity as well as cellular levels of p53 by 15d-PGJ2.
p53 mcf-7 cells 15-deoxy-?12 14-prostaglandin j2 human breast cancer cells