Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Evid Based Complement Alternat Med. 2015;2015:921306. doi: 10.1155/2015/921306. Epub 2015 Apr 9.
We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer.
我们研究了黄腐酚对 Ca Ski 宫颈癌细胞系诱导细胞凋亡的作用。黄腐酚是一种天然存在于啤酒花植物中的类查尔酮,先前有报道称它是各种癌细胞系中的一种有效抗癌剂。本研究表明,黄腐酚通过磺基罗丹明 B(SRB)测定法抑制 Ca Ski 细胞增殖的 IC50 值有效。此外,还通过相差显微镜和 Hoechst/PI 荧光染色观察细胞的形态变化。此外,黄腐酚处理 48 小时后,可引发细胞中磷脂酰丝氨酸外翻、线粒体膜电位变化和 DNA 片段化。此外,黄腐酚介导的细胞周期分析中的 S 期阻滞和 caspase-3、caspase-8 和 caspase-9 的活性增加。另一方面,Western blot 分析表明,PARP 蛋白、p53 和 AIF 的表达水平呈剂量依赖性增加,而 Bcl-2 和 XIAP 减少。综上所述,这些发现表明黄腐酚诱导的细胞死亡可能涉及内在和外在的凋亡途径,以及 XIAP 的下调、p53 蛋白的上调和 Ca Ski 宫颈癌细胞的 S 期细胞周期阻滞。这项工作表明黄腐酚是治疗宫颈癌的有效化学治疗候选药物。