In general, the data suggest that inhibition of PDF by actinonin has a greater effect on proliferation of cancer cells compared to normal cells. PDF mRNA is elevated in many cancer tissues TissueScanTM Cancer qPCR Arrays containing cDNA from 96 tissue samples representing eight different cancers were SB203580 HCC used to determine PDF expression in cancer com pared to non cancer tissues. For each tissue type, the array contained 3 normal control tissues and 9 cancer tissues. With the exception of liver cancer that showed to non cancer cells. The IC50s were Inhibitors,Modulators,Libraries 19. 3, 17. 3, and 113. 5 uM for the Hs578T, HT 29, and PC 3 cancer cell lines, respectively while the IC50s were 208, 31. 9, and 207. 4 uM for the Hs578Bst, CCD 18Co, and PrEC cells, respectively.

While the IC50 was higher in the normal colon compared to the colon cancer cell Inhibitors,Modulators,Libraries line, the difference in the percentage of viable cells was not statistically significant. In contrast, actinonin significantly affected the growth of breast and prostate cancer cells no change compared to control liver samples, PDF was at Inhibitors,Modulators,Libraries least slightly elevated in all cancer tissues compared to control, and PDF mRNA levels were significantly Inhibitors,Modulators,Libraries elevated in the breast, colon, and lung cancer tissue samples compared to their non cancer samples. Breast cancer showed a 5. 8 fold increase in expression of PDF while colon and lung showed a 3. 5 and 3. 4 fold increase in PDF expression, respectively. Additional tissue panels for breast, colon, and lung cancer patients were used to validate the previous results and to assess MAP1D levels in these cancer types.

Colon and lung tissue panels contained 48 matched normal and cancer tissue Inhibitors,Modulators,Libraries samples from 24 cancer patients while the breast tissue panels contained 48 unmatched tissue samples that included 12 normal breast tissue controls and 36 breast cancer samples at various disease stages. Similar to the first results, PDF was elevated in breast, colon, and lung cancer samples and showed stage dependent expression with the highest expression in late stage breast cancer, but early stage colon and lung cancers. MAP1D mRNA expression was elevated in early stage colon cancer samples, and was surprisingly reduced in breast cancer samples compared to control samples. There was no significant change in MAP1D mRNA levels in lung cancer samples at any stage compared to control.

These results suggest PDF and MAP1D expression is altered in certain cancer tissues and that expression of these enzymes is correlated with the stage of disease. PDF protein levels www.selleckchem.com/products/FTY720.html are elevated in colon cancer tissues To verify that the increased PDF mRNA levels translated to increased PDF protein levels, we screened two sets of colon cancer tissues for PDF expression. Matched colon cancer and normal colon tissue sets were obtained from two pa tients at the VA Hospital in Fargo, ND in accordance with IRB policies.