| Abstrak/Abstract |
Previous study has reported that colon cancer can be blocked by anti-inflammatory drugs trough the down regulation of cyclooxygenase 2 (COX 2) expression by which they capable of inducing apoptosis. Two analogues of curcumin, PGV-0 (2,5-bis-(4?-hydroxy-3-methoxy)-benzilidine-cyclopentanone) and PGV-1 (2,5-bis-(4-hydroxy,3,5-dimethyl)-benzilidine-cyclopentanone) have the better potencies of anti-inflammatory effects than curcumin. Both PGV-0 and PGV-1 also show the much stronger inhibition of COX 2 activities than curcumin and aspirin in vivo. In this study, the COX 2 inhibition and apoptosis induction effects of PGV-0 and PGV-1 in WiDr colon cancer cell line were explored to discover potent chemopreventive agents for cancer colon treatment. Induction of pro-apoptotic protein Bax expression was also examined to understand the role of another mechanism of apoptosis induction. The result showed that IC50 values of PGV-0 and PGV-1 in WiDr cell determined by MTT assay were 45 ?M and 8 ?M, respectively. Moreover, evidence of apoptosis examined by double staining with ethidium bromide-acrydine orange indicated that both PGV-0 and PGV-1 caused apoptotic bodies at inhibitory concentrations. On the other hand, immunocytochemistry assay indicated that PGV-0 significantly decreased COX 2 expression, but contradictory PGV-1 did not show any inhibition. PGV-0 also induced higher Bax expression than PGV-1. These findings suggest that PGV-1 is the most prospective chemopreventive agent although it acted via independent inhibition of COX 2 expression pathway. Therefore, further mechanism of growth inhibition and apoptosis induction of PGV-1 is important to be explored. |
