Time filter

Source Type

Wu J.-Y.,National Chiayi University | Tsai K.-W.,Buddhist Tzuchi Dalin General Hospital | Shee J.-J.,Chang Gung Memorial Hospital | Li Y.-Z.,National Chiayi University | And 3 more authors.
Acta Pharmacologica Sinica | Year: 2010

Aim: To examine the antitumor effect of 4′-chloro-3,5- dihydroxystilbene, a resveratrol derivative, on lung adenocarcinoma A549 cells.Methods:The cytotoxic IC50 was determined by direct cell counting. Flow cytometry,monodansylcadaverine (MDC) staining, transfection, Western blot and a proteasome activity assay were used to study the cellular mechanism of 4′-chloro-3,5-dihydroxystilbene. A xenograft nude mouse model was used to analyze the antitumor effect invivo.Results:4′-Chloro-3,5- dihydroxystilbene induced a rapid and persistent increase in the intracellular reactive oxygen species in the cells, but the cell death could not be inhibited by two antioxidant agents. The derivative caused sub-G1 formation, a decrease in the mitochondria membrane potential and poly (ADP-ribose) polymerase degradation, and the caspase inhibitor Z-VAD-FMK could partially prevent cell death. It also induced a significant increase in intracellular acidic vacuoles, LC3-II formation and intracellular GFP-LC3 aggregation. An autophagic inhibitor partially reversed cell death. Additionally, 4′-chloro-3,5- dihydroxystilbene induced the accumulation of ubiquitinated conjugates and inhibited proteasome activity in cells. In an in vivo study, 4′-chloro-3,5-dihydroxystilbene retarded tumor growth in nude mice.Conclusion: These data suggest that the resveratrol derivative 4′-chloro-3,5-dihydroxystilbene could be developed as an anti-tumor compound. © 2010 CPS and SIMM All rights reserved.

Wu J.-Y.,National Chiayi University | Tsai K.-W.,Buddhist Tzuchi Dalin General Hospital | Li Y.-Z.,National Chiayi University | Chang Y.-S.,National Chiayi University | And 4 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2013

Some phytochemicals with the characteristics of cytotoxicity and/or antimetastasis have generated intense interest among the anticancer studies. In this study, a natural flavonoid baicalein was evaluated in bladder cancer in vitro and in vivo. Baicalein inhibits 5637 cell proliferation. It arrests cells in G1 phase at 100 M and in S phase below 75 M. The protein expression of cyclin B1 and cyclin D1 is reduced by baicalein. Baicalein-induced p-ERK plays a minor role in cyclin B1 reduction. Baicalein-inhibited p65NF-B results in reduction of cell growth. Baicalein-induced pGSK(ser9) has a little effect in increasing cyclin B1/D1 expression instead. The translation inhibitor cycloheximide blocks baicalein-reduced cyclin B1, suggesting that the reduction is caused by protein synthesis inhibition. On the other hand, neither cycloheximide nor proteasome inhibitor MG132 completely blocks baicalein-reduced cyclin D1, suggesting that baicalein reduces cyclin D1 through protein synthesis inhibition and proteasomal degradation activation. In addition, baicalein also inhibits cell invasion by inhibiting MMP-2 and MMP-9 mRNA expression and activity. In mouse orthotopic bladder tumor model, baicalein slightly reduces tumor size but with some hepatic toxicity. In summary, these results demonstrate the anti-bladder-tumor properties of the natural compound baicalein which shows a slight anti-bladder-tumor effect in vivo. © 2013 Jin-Yi Wu et al.

Discover hidden collaborations