Lee Sau K, Zhang Wei, Sanderson Barbara J S
Department of Medical Biotechnology, School of Medicine, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia.
J Agric Food Chem. 2008 Aug 27;56(16):7572-7. doi: 10.1021/jf801014p. Epub 2008 Jul 26.
There is great interest in the potential chemopreventive activity of resveratrol against human cancers. However, there are conflicting results on its growth inhibitory effect on normal cells. This project examined the differential effect of resveratrol at physiologically relevant concentrations on nonmalignant (WIL2-NS) and malignant (HL-60) cell lines and compared the underlying mechanisms via cell cycle modulation, apoptosis induction, and genotoxicity potential. Twenty-four hours of exposure to resveratrol was toxic to WIL2-NS and HL-60 cells in a dose-dependent manner. WIL2-NS cells regrew 5 times more than HL-60 cells by 120 h after the removal of 100 microM resveratrol (p < 0.05). Furthermore, significant alterations in cell cycle kinetics were induced by resveratrol in HL-60 cells, but were to a lesser extent for WIL2-NS cells. The proportion of apoptosis was also 3 times higher in HL-60 cells as compared to WIL2-NS cells for 100 microM resveratrol (p < 0.05). In conclusion, resveratrol preferentially inhibited the growth of HL-60 cells via cell cycle modulation and apoptosis induction and subsequently directed the cells to irreversible cell death, whereas the effect on WIL2-NS cells was largely reversible.
白藜芦醇对人类癌症的潜在化学预防活性引起了极大关注。然而,关于其对正常细胞生长抑制作用的结果却相互矛盾。本项目研究了生理相关浓度下白藜芦醇对非恶性(WIL2-NS)和恶性(HL-60)细胞系的差异作用,并通过细胞周期调控、凋亡诱导和遗传毒性潜能比较了潜在机制。暴露于白藜芦醇24小时对WIL2-NS和HL-60细胞具有剂量依赖性毒性。去除100微摩尔白藜芦醇后120小时,WIL2-NS细胞的再生长速度比HL-60细胞快5倍(p<0.05)。此外,白藜芦醇在HL-60细胞中诱导了细胞周期动力学的显著改变,但对WIL2-NS细胞的影响较小。对于100微摩尔白藜芦醇,HL-60细胞的凋亡比例也比WIL2-NS细胞高3倍(p<0.05)。总之,白藜芦醇通过细胞周期调控和凋亡诱导优先抑制HL-60细胞的生长,并随后引导细胞走向不可逆的细胞死亡,而对WIL2-NS细胞的影响在很大程度上是可逆的。