Modulation of the constitutive activated STAT3 transcription factor in pancreatic cancer prevention: effects of indole-3-carbinol (I3C) and genistein.

The signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor required in proliferation and differentiation. STAT3 is activated constitutively in a number of cancers.This study was conducted to assess the possible involvement of STAT3 activation in pancreatic cancer and the potential for this pathway as a target in chemopreventive strategy.STAT3 was shown for the first time to be constitutively activated in human pancreatic carcinoma specimens but not in normal pancreatic tissues. Constitutively activated STAT3 was also found in pancreatic tumor cell lines (Panc-1 and MIA PaCa-2) which could be modulated by indole-3-carbinol (13C) and genistein. At concentrations higher than 10 microM, STAT3 constitutive activation is inhibited by both agents. Induction of apoptosis by 13C was also demonstrated.Given its critical role in tumorigenesis, our results suggest that STAT3 activation provides an important and appropriate target for chemoprevention in pancreatic cancer treatment.