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Abstract Title:

4'-Chloro-3,5-dihydroxystilbene, a resveratrol derivative, induces lung cancer cell death.

Abstract Source:

Acta Pharmacol Sin. 2010 Jan;31(1):81-92. PMID: 20048747

Abstract Author(s):

Jin-yi Wu, Kun-wei Tsai, Jia-jen Shee, Yi-zhen Li, Ching-hsein Chen, Jing-jing Chuang, Yi-wen Liu

Article Affiliation:

Graduate Institute of Biomedical and Biopharmaceutical Sciences, National Chiayi University, Chiayi, Taiwan, China.

Abstract:

AIM: To examine the antitumor effect of 4'-chloro-3,5-dihydroxystilbene, a resveratrol derivative, on lung adenocarcinoma A549 cells.

METHODS: The cytotoxic IC(50) 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 in vivo.

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-G(1) 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.

Study Type : Transgenic Animal Study

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