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

   
@article{APS4512,
	author = {Jin-yi Wu and Kun-wei Tsai and Jia-jen Shee and Yi-zhen Li and Ching-hsein Chen and Jing-jing Chuang and Yi-wen Liu},
	title = {4’-Chloro-3,5-dihydroxystilbene, a resveratrol derivative, induces lung cancer cell death},
	journal = {Acta Pharmacologica Sinica},
	volume = {31},
	number = {1},
	year = {2016},
	keywords = {},
	abstract = {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 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-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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4512}
}