Suppression of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity by resveratrol derivatives

As demonstrated previously, resveratrol (3,4',5-trihydroxy-trans-stilbene) inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC), the key rate limiting enzyme in mammalian polyamine synthesis. Using human bladder epithelial carcinoma HTB-24 cells in culture where resveratrol inhibits induction with an IC50 of 8.8 µM, we now report potential metabolites demonstrate greater activity [tetrabutylammonium (E)-4-(3,5-dihydroxystyryl)phenyl sulfate (IC50 1.2 µM), resveratrol tripotassium 3,5,4'-trisulfate (IC50 1.8 µM), resveratrol tripotassium 3,4'-disulfate (IC50 1.8 µM), and resveratrol tripotassium 3,5-disulfate (IC50 2.3 µM)]. Based on RT-PCR studies, ODC inhibition occurs at the transcriptional level, but this was not due to direct inhibition of protein kinase C (e.g., resveratrol IC50, 79 µM; resveratrol tripotassium 3,5-disulfate IC50, 49 µM). Additional work is underway to more fully investigate this potentially important observation. [This work was supported by program project P01 CA48112 awarded by the National Cancer Institute. SL acknowledges Indo-US Science and Technology Forum (IUSSTF), New Delhi for a Research Fellowship]