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Pancreatic cancer is the fourth cause of death in the U.S. Due to its aggressive and resistance characteristics, prognosis is often fatal. Inactivation of tumor suppressor genes such as p53 and p16 early in the carcinogenesis process allows the selective advantage of other genomic changes and damage to occur, which further contributes to its progression. p16 inactivation through promoter hypermethylation is an early event in this process. PCR analyses of pancreatic cancer cells (MIA PaCa-2) treated with 1, 10 or 100 μM of I3C demonstrated reactivation of p16 at 10 or 100 μM, both at 24 and 48 hrs. p16 was not expressed in the untreated control. Methylated-sensitive-PCR (MSP) analyses demonstrated that indole-3-carbinol unmethylated the promoter region of p16, which was methylated in the untreated control. A positive control using 5-azacytidine also reactivated p16 at 48 hrs, but not 24 hrs. Recent data published in our laboratory demonstrated that I3C significantly decreased the expression of DNA methyltransferases (Haefele, et.al., International J Cancer Prev., 2(4):245-255, 2007). This study showed the potential use of the dietary agent, I3C, as a hypomethylating agent in chemopreventive or therapeutic strategies for pancreatic cancer.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA