Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines
Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines
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DOI：
10.1007/s13277-015-3689-3
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Dodurga, Yavuz
中科院分区：
文献类型：
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作者：
Eroglu, Canan;Secme, Mucahit;Dodurga, Yavuz
对前列腺癌的基因变化和可能的信号通路的研究日益增多，新的治疗方法也在不断探索中。本研究旨在探讨酚类化合物阿魏酸（FA）对PC-3和LNCaP前列腺癌细胞的细胞周期、凋亡、侵袭和集落形成的影响。采用2,3-二-（2-甲氧基-4-硝基-5-磺胺基）- 2h -四氮唑-5-羧基苯胺（XTT）法测定FA对细胞活力的影响。用Tri Reagent分离总RNA。采用逆转录酶PCR （RT-PCR）检测84个细胞周期和凋亡相关基因的表达。Western blot检测蛋白表达。此外，用末端脱氧核苷酸转移酶脱氧尿苷三磷酸缺口端标记法（TUNEL）观察FA对细胞凋亡的影响。采用基质室法和集落法分别测定FA对细胞侵袭和集落形成的影响。FA对PC-3细胞的半数最大抑制浓度（IC50）为300 μ M，对LNCaP细胞的半数最大抑制浓度为500 μ M。RT-PCR结果显示，FA通过增加PC-3细胞中ATR、ATM、CDKN1A、CDKN1B、E2F4、RB1、TP53基因的表达，降低CCND1、CCND2、CCND3、CDK2、CDK4、CDK6基因的表达来抑制细胞增殖。另一方面，FA通过增加LNCaP细胞中CASP1、CASP2、CASP8、CYCS、FAS、FASLG和TRADD基因的表达，降低BCL2和XIAP基因的表达来抑制细胞增殖。在本研究中，CDK4和BCL2基因的蛋白表达在这些细胞中显著降低。可诱导PC-3和LNCaP细胞凋亡。此外，FA还能抑制PC-3和LNCaP细胞的侵袭。此外，它还抑制了蜂群的形成。综上所述，FA在PC-3细胞中可能导致细胞周期阻滞，而在LNCaP细胞中可能导致细胞凋亡。
Studies on genetic changes underlying prostate cancer and the possible signaling pathways are getting increased day by day, and new treatment methods are being searched for. The aim of the present study is to investigate the effects of ferulic acid (FA), a phenolic compound, on cell cycle, apoptosis, invasion, and colony formation in the PC-3 and LNCaP prostate cancer cells. The effect of FA on cell viability was determined via a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method. Total RNA was isolated with Tri Reagent. Expression of 84 genes for both cell cycle and apoptosis separately was evaluated by reverse transcriptase PCR (RT-PCR). Protein expressions were evaluated by Western blot analysis. Furthermore, apoptotic effects of FA were observed with terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assay. Effects of FA on cell invasion and colony formation were determined using Matrigel chamber and colony assay, respectively. The half maximal inhibitory concentration (IC50) dose of FA was found to be 300 mu M in PC-3 cells and 500 mu M in LNCaP cells. According to RT-PCR results, it was observed that FA inhibited cell proliferation by increasing the gene expressions of ATR, ATM, CDKN1A, CDKN1B, E2F4, RB1, and TP53 and decreasing the gene expressions of CCND1, CCND2, CCND3, CDK2, CDK4, and CDK6 in PC-3 cells. On the other hand, it was seen that FA suppressed cell proliferation by increasing in the gene expressions of CASP1, CASP2, CASP8, CYCS, FAS, FASLG, and TRADD and decreasing in the gene expressions of BCL2 and XIAP in LNCaP cells. In this study, protein expression of CDK4 and BCL2 genes significantly decreased in these cells. It could induce apoptosis in PC-3 and LNCaP cells. Also, it was observed that FA suppressed the invasion in PC-3 and LNCaP cells. Moreover, it suppressed the colony formation. In conclusion, it has been observed that FA may lead to cell cycle arrest in PC-3 cells while it may cause apoptosis in LNCaP cells.