Effects of Psoralen as an Anti-tumor Agent in Human Breast Cancer MCF-7/ADR Cells
Effects of Psoralen as an Anti-tumor Agent in Human Breast Cancer MCF-7/ADR Cells
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DOI：
10.1248/bpb.b15-00957
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发表时间：
2016-05-01
影响因子：
2
通讯作者：
Yang, Zhenlin
中科院分区：
文献类型：
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作者：
Wang, Xiaohong;Cheng, Kai;Yang, Zhenlin
补骨脂素是补骨脂的主要活性成分。在本研究中，我们分析了人乳腺癌MCF-7/ADR细胞中的紫杉醇诱导的变化，并研究了对MCF-7/ADR细胞的抗癌作用的潜在机制。我们通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四氮唑溴化物（MTT）法检测细胞活力，以评估peptide的细胞毒性和多药耐药（MDR）逆转活性。流式细胞仪检测PdR处理后MCF-7/ADR细胞的细胞周期分布、细胞凋亡、罗丹明123（Rh 123）的积累和外排以及P-糖蛋白（P-gp）的表达水平。我们通过监测ATP消耗来评估P-gp ATP酶活性。我们评估了参与调节上皮间质转化（EMT）的核因子-κ B（NF-κ B）的活性以及E-钙粘蛋白、波形蛋白和α-平滑肌肌动蛋白（SMA）的表达。结果表明，苦参素抑制MCF-7/ADR细胞增殖，表现为G 0/G1期阻滞，而不是促进细胞凋亡。P-gp的表达与ATP酶活性无关，P-gp的表达与ATP酶活性无关，P-gp的表达与ATP酶活性无关。结果进一步表明，补骨脂素可能通过抑制NF-κ B B的活化，抑制EMT，从而抑制MCF-7/ADR细胞的迁移能力。本研究结果为进一步探索天然化合物作为新型抗癌药物提供了系统和详细的描述。
Psoralen is a major active component of Psoralea corylifolia. In the present study, we analyzed psoralen-induced changes in human breast cancer MCF-7/ADR cells and investigated the underlying mechanisms of the anticancer effect on MCF-7/ADR cells. We measured cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide (MTT) assay to evaluate the cytotoxicity and multidrug resistance (MDR) reversal activity of psoralen. The cell cycle distribution and apoptosis, accumulation and efflux of rhodamine123 (Rh123), and P-glycoprotein (P-gp) expression levels of MCF-7/ADR cells treated with psoralen were all detected by flow cytometry (FCM). We assessed P-gp ATPase activity by monitoring ATP consumption. We evaluated the activity of nuclear factor-kappaB (NF-kappa B) and the expression of E-cadherin, vimentin and alpha-smooth muscle actin (SMA) involved in regulating epithelial mesenchymal transition (EMT). The results showed that psoralen inhibited the proliferation of MCF-7/ADR cells as shown by G0/G1 phase arrest rather than encouraging apoptosis. It was also observed that psoralen reversed MDR through inhibiting ATPase activity rather than reducing P-gp expression. Our results further showed that psoralen inhibited the migration abilities of MCF-7/ADR cells by repressing EMT possibly through inhibiting the activation of NF-kappa B. Our findings provided a systematic and detailed description of the anti-cancer effect of psoralen on MCF-7/ADR cells for the exploration of natural compounds as novel anticancer agents.