Pancreatic cancer is a very aggressive malignant disease due to lack of early diagnosis and chemotherapeutic resistance of the
tumor cells. There is distinct evidence that food derived
polyphenols possess chemopreventive effects in the development of several
cancers including
pancreatic carcinoma.
Resveratrol is one of those phenolic compounds found in grape skins and other fruits with known anticancer activity. Various polymethoxylated
resveratrol derivatives showed stronger antiproliferative effects than
resveratrol in tumor cell lines. The aim of our study was to evaluate the cytotoxic and biochemical effects of a newly synthesized polymethoxylated
resveratrol analogue, N-hydroxy-N'-(3,4,5-trimethoxphenyl)-3,4,5-trimethoxy-benzamidine (KITC) in two human
pancreatic cancer cell lines. The human
pancreatic cancer cell lines, AsPC-1 and BxPC-3 were used to test the potential inhibitory effect of the
resveratrol derivative on cell proliferation and the underlying mechanisms of this effect. After 7 days of incubation, KITC inhibited the growth of AsPC-1 and BxPC-3 cells with IC(50) values of 9.6 and 8.7 microM, respectively. KITC (40 microM) arrested cells in the G0/G1 phase and depleted cells in the S phase of the cell cycle (-105% and -35% of control, respectively). KITC induced dose-dependent apoptosis in both
pancreatic cancer cell lines and was found to significantly reduce the in situ activity of
ribonucleotide reductase, the key
enzyme of
DNA synthesis. Employing growth inhibition assays, KITC acted synergistically with
gemcitabine in both cell lines. In summary, we found that KITC exerted considerable antitumor activity against human
pancreatic cancer cells and could be a promising candidate for further investigations to establish a new chemotherapeutic regimen.