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首页> 外文OA文献 >Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells
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Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells

机译：几种香豆素对人癌细胞系细胞毒性和凋亡作用的比较评价：胞肠诱导P53缺陷H1299细胞凋亡

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摘要

Natural products are excellent resources for finding lead structures for the development of chemotherapeutic agents. Coumarins are a class of natural compounds found in a variety of plants. In this study, we evaluated the cytotoxic potential of coumarins isolated from Prangos ferulacea (L.) Lindl. in PC3, SKNMC, and H1299 (p53 null) human carcinoma cell lines. Osthole proved to be an outstanding potent cytotoxic agent especially against PC3 cells. Isoimperatorin exhibited moderate inhibitory effect against SKNMC and PC3 cell lines. Oxypeucedanin and braylin did not display any cytotoxic activity. In the next set of experiments, the apoptotic potentials of osthole and isoimperatorin were investigated. Induction of apoptosis by isoimperatorin was accompanied by an increase in activation of caspase-3, -8, and -9 in SKNMC cells and caspase-3 and -9 in PC3 cells. Moreover, isoimperatorin induced apoptosis by upregulating Bax and Smac/DIABLO genes in PC3 and SKNMC cells. Osthole induced apoptosis by downregulating antiapoptotic Bcl-2 in only PC3 cells and upregulating the proapoptotic genes Bax and Smac/DIABLO in PC3, SKNMC, and H1299 cells. The effects of osthole on H1299 cells are important because the loss of p53 has been associated with poor clinical prognosis in cancer treatment.
机译：天然产品是寻找化学治疗剂的发展铅结构的优异资源。香豆素是一类在各种植物中发现的天然化合物。在这项研究中，我们评估了来自Prangos Ferulacea（L.）Lindl的香豆素的细胞毒性潜力。在PC3，SKNMC和H1299（P53零）人类癌细胞系中。 Esthole被证明是一种突出的有效细胞毒性剂，尤其是对PC3细胞。胰岛素素对SknMC和PC3细胞系具有中度抑制作用。 OxypeuceAnin和Braylin没有显示任何细胞毒性活性。在下一组实验中，研究了胞孔和异叶酸素的凋亡势。胰岛素诱导诱导凋亡伴有Caspase-3，-8和-9中的SKNMC细胞和Caspase-3和-9中的诱导伴随着PC3细胞中的Caspase-3，-8和-9。此外，通过在PC3和SKNMC细胞中上调BAX和SMAC /暗黑破坏神基因来诱导胰岛素诱导细胞凋亡。通过仅在PC3细胞中下调抗曝光Bcl-2并在PC3，SKNMC和H1299细胞中诱导抗曝光Bcl-2并将凋亡基因Bax和Smac /暗黑破坏瘤诱导细胞凋亡。汤孔对H1299细胞的影响很重要，因为P53的损失与癌症治疗中的临床预后差有关。

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