DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line.
DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line.
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DOI：
10.4103/0970-1591.117278
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Shabestari MM
中科院分区：
文献类型：
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作者：
Samarghandian S;Shabestari MM
细胞凋亡是导致细胞生长抑制的一个重要机制，据报道，番红花在不同的癌症类型中都有诱导细胞凋亡的作用。然而，将这些影响与藏红花的有效成分联系起来的努力有限。本研究旨在阐明藏红花中的主要着色物藏红花对人前列腺癌PC-3细胞株的细胞毒作用和诱导细胞凋亡的作用。培养PC-3和人胎肺成纤维细胞，加入5、10、15和20μg/ml的藏红花。采用四甲基偶氮唑蓝(3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)比色法检测细胞毒性。凝胶电泳法检测DNA片段化程度。用不同浓度的藏红花与细胞孵育，分别用普通倒置显微镜、Annexin V和碘化丙啶检测细胞形态变化和细胞凋亡率，然后用流式细胞仪分析。四甲基偶氮唑盐比色法显示，藏红花对PC-3细胞有明显的细胞毒作用，且呈浓度依赖性。细胞的形态变化证实了四甲基偶氮唑蓝的结果。48h和72h对PC-3细胞的IC50值分别为13.00.07和6.40.09μg/ml。在处理细胞的流式细胞仪直方图中，藏红花诱导了早期和晚期的细胞凋亡，表明细胞凋亡参与了这种毒性。DNA分析最早在治疗后48h和72h出现典型的梯形条带，表明细胞发生了凋亡。我们的临床前研究表明，前列腺癌细胞系对藏红花介导的生长抑制和凋亡细胞死亡高度敏感。尽管藏红花作用的分子机制尚不清楚，但它似乎具有作为治疗剂的潜力。
Apoptosis, an important mechanism that contributes to cell growth reduction, is reported to be induced by Crocus sativus (Saffron) in different cancer types. However, limited effort has been made to correlate these effects to the active ingredients of saffron. The present study was designed to elucidate cytotoxic and apoptosis induction by safranal, the major coloring compound in saffron, in a human prostate cancer cell line (PC-3). PC-3 and human fetal lung fibroblast (MRC-5) cells were cultured and exposed to safranal (5, 10, 15, and 20 μg/ml). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to assess cytotoxicity. DNA fragmentation was assessed by gel electrophoresis. Cells were incubated with different concentrations of safranal, and cell morphologic changes and apoptosis were determined by the normal inverted microscope, Annexin V, and propidium iodide, followed by flow cytometric analysis, respectively. MTT assay revealed a remarkable and concentration-dependent cytotoxic effect of safranal on PC-3 cells in comparison with non-malignant cell line. The morphologic alterations of the cells confirmed the MTT results. The IC50 values against PC-3 cells were found to be 13.0 0.07 and 6.4 0.09 μg/ml at 48 and 72 h, respectively. Safranal induced an early and late apoptosis in the flow cytometry histogram of treated cells, indicating apoptosis is involved in this toxicity. DNA analysis revealed typical ladders as early as 48 and 72 h after treatment, indicative of apoptosis. Our preclinical study demonstrated a prostate cancer cell line to be highly sensitive to safranal-mediated growth inhibition and apoptotic cell death. Although the molecular mechanisms of safranal action are not clearly understood, it appears to have potential as a therapeutic agent.