Effect of Indole-3-Carbinol on Inhibition of MMP Activity via MAPK Signaling Pathway in Human Prostate Cancer Cell Line, PC3 Cells

We examined the effect of indole-3-carbinol (I3C, C9H9NO), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, on MMP-2, -9 activities and TIMP-1 and -2 inductions via microtubule-associated protein kinase (MAPK) signaling pathway in prostate cancer cell line, PC3 cells. Our results indicated that I3C inhibited cell growth of PC3 cells in dose (0, 50, 100 micrometer) and time (0, 24, 48 and 72 h) dependent manners. Using gelatin zymography for MMP activity, we demonstrated that I3C significantly decrease MMP-2 and -9 activities in PC3 cells. We also observed that I3C decreased the proteins and mRNA levels of MMP-2 and -9 in PC3 cells as well. Inversely, expressions of TIMP-1 and -2 protein and mRNA in PC3 cells were increased by I3C in a dose dependent manner. In another experiment, we showed that I3C inhibited PC3 cells invasiveness by using marigel invasion assay and we also found that I3C suppressed MMP transcriptional activity by MAPK signaling pathways. Taken together, our results suggest that I3C may contribute to the potential beneficial food component to prevent the cancer metastasis in prostate cancer cells.

Indol-3-Carbinol Regulated Tight Junction Permeability and Associated-Protein Level and Suppressed Cell Invasion in Human Colon Cancer Cell Line, HT-29

To determine whether indol-3-carbinol (I3C, C9H9NO), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, regulated tight junction proteins (TJ) and suppressed cell invasion in colon cancer cells,this experiment was performed. Our results indicate that I3C inhibit cell growth of HT-29 cells in a dose (0, 50, 100 micrometer) and time (0, 24 and 48 h) dependent manner. Using the wound healing and matrigel invasion study, respectively, I3C inhibits the cell motility and invasion of the ovarian cancer cell line. The TEER values were increased in HT-29 cells grown in transwells treated with I3C, reversely, paracellular permeability was decreased in those of condition. Claudin-1, claudin-5, ZO-1 and occuldin have been shown to be positively expressed in HT-29 coloncancer cells. I3C occurs concurrently with a significant decrease in the levels of those of proteins in HT-29 cells. But E-cadherin level in the HT-29 was increased by I3C. The reduction of claudin-1 and claudin-5 protein levels occurred post-transcriptionaly since their mRNA levels are no difference by I3C. Therefore, our results suggest that I3C may be expected to inhibit cancer metastasis and invasion by tighten the cell junction and restoring tight junction in colon cancer cell line, HT-29.