Role of STAT3-Interacting Protein (STIP1) in Δ<SUP>12</SUP>-Prostaglandin J<SUB>2</SUB>-Induced Cell Death

Role of STAT3-Interacting Protein (STIP1) in Δ<SUP>12</SUP>-Prostaglandin J<SUB>2</SUB>-Induced Cell Death

Δ<SUP>12</SUP>-Prostaglandin J<SUB>2</SUB> (Δ<SUP>12</SUP>-PGJ<SUB>2</SUB>) is one of cyclopentenone prostaglandins. The Δ<SUP> 12</SUP>-PGJ<SUB>2</SUB> is known to induce apoptosis of tumor cells, however, it s action mechanism is not clear. It has recently been reported that STAT3 is involved in tumorigenesis. In the present study, we investigated the role of STAT3-interacting protein (STIP1) in the cytotoxicity of Δ<SUP> 12</SUP>-PGJ<SUB>2</SUB>, since STIP1 was recently reported as a modulator of STAT3 activation by specifically binding to inactive (unphosphorylated) STAT3. The effect of Δ<SUP>12</SUP>-PGJ<SUB>2</SUB> was observed in stably overexpressing Neuro-2A cells transfected with full cDNA of STIP1, and cytotoxicity of Δ<SUP> 12</SUP>-PGJ<SUB>2</SUB> in the transfected cells was increased, compared with the vector control cells. The cytotoxicity of Δ<SUP>12</SUP>-PGJ<SUB>2</SUB> treatment was significantly accentuated by pretreatment of the STIP1-transfected cells with protein kinase inhibitor, genistein, and less activation of STAT3 in STIP1-transfected cells was shown, compared with the vector control cells. Expression of bax was also increased in the STIP1-transfected cells. These data suggest that STIP1 inhibits cell growth via inhibition of STAT3 activation in Δ<SUP>12</SUP>-PGJ<SUB>2</SUB> treatment.