Department of Obstetrics and Gynecology, Chung ShanMedical University Hospital, Taichung, Taiwan.
Arch Toxicol. 2012 Feb;86(2):263-73. doi: 10.1007/s00204-011-0754-6. Epub 2011 Oct 1.
Fisetin is a naturally occurring flavonoid that has been reported to inhibit the proliferation and to induce apoptotic cell death in several tumor cells. However, the apoptosis-inducing effect of fisetin on tumor cell lines was investigated besides HeLa cells. In this study, we found that fisetin induced apoptosis of HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining of 4'-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI double-labeling. In addition, fisetin triggered the activations of caspases-3 and -8 and the cleavages of poly (ADP-ribose) polymerase, resulting in apoptosis induction. Moreover, treatment of HeLa cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059 (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector significantly abolished the fisetin-induced apoptosis through the activation of caspase-8/-3 pathway. The in vivo xenograft mice experiments revealed that fisetin significantly reduced tumor growth in mice with HeLa tumor xenografts. In conclusion, our results indicated that fisetin exhibited anti-cancer effect and induced apoptosis in HeLa cell lines both in vitro and in vivo.
漆黄素是一种天然存在的类黄酮，据报道，它能抑制几种肿瘤细胞的增殖并诱导其凋亡。然而，除了 HeLa 细胞之外，漆黄素对肿瘤细胞系的凋亡诱导作用尚未得到研究。在这项研究中，我们发现，漆黄素能以剂量和时间依赖的方式诱导 HeLa 细胞凋亡，这一点可以通过 4'-6-二脒基-2-苯基吲哚（DAPI）核染色、流式细胞术分析和 Annexin-V/PI 双标记来证明。此外，漆黄素触发了 caspase-3 和 -8 的激活以及多聚（ADP-核糖）聚合酶的裂解，从而诱导了凋亡。此外，用漆黄素处理 HeLa 细胞会持续激活 ERK1/2 的磷酸化，而 PD98059（MEK1/2 抑制剂）的处理或转染突变型 ERK1/2 表达载体显著通过激活 caspase-8/-3 途径而消除了漆黄素诱导的凋亡。体内异种移植小鼠实验表明，漆黄素能显著减少荷有 HeLa 肿瘤异种移植的小鼠的肿瘤生长。总之，我们的结果表明，漆黄素在体外和体内均表现出抗癌作用并诱导 HeLa 细胞系发生凋亡。
