Apigenin affects leptin/leptin receptor pathway and induces cell apoptosis in lung adenocarcinoma cell line
Apigenin affects leptin/leptin receptor pathway and induces cell apoptosis in lung adenocarcinoma cell line
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DOI：
10.1016/j.ejca.2011.03.034
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发表时间：
2011-09-01
影响因子：
8.4
通讯作者：
Pace, Elisabetta
中科院分区：
文献类型：
--
作者：
Bruno, Andreina;Siena, Liboria;Pace, Elisabetta
背景：芹菜素是一种常见的食用植物类黄酮，是一种具有良好特性的抗氧化剂。脂肪因子瘦素在多种细胞类型中发挥增殖和抗凋亡活性。在癌细胞中，芹菜素可能诱导促凋亡途径，而瘦素具有抗凋亡作用。本研究旨在探讨芹菜素和瘦素/瘦素受体通路在肺腺癌增殖和凋亡中的作用。方法：采用免疫细胞化学、流式细胞仪和RT-Q-RT-PCR方法，观察在芹菜素和瘦素单独或联合作用下，肺腺癌细胞株A549上瘦素受体的表达和调控。用克隆形成试验评价细胞增殖情况。流式细胞仪检测外源性瘦素与其受体的结合，二氯二乙酸荧光素分析细胞内活性氧(ROS)，溴化乙锭诱导细胞死亡，Annexin V分析细胞凋亡。结果：A549细胞表达瘦素/瘦素受体通路，芹菜素可上调其表达。芹菜素单独或联合瘦素显著抑制细胞增殖，显著增加ROS的自发释放，增加细胞死亡和凋亡，后者在肺腺癌PF中也存在。单用瘦素可显著促进细胞增殖，显著降低细胞死亡率。结论：这些结果有力地提示了黄酮类芹菜素在肺腺癌患者辅助治疗中的潜在用途。(C)2011爱思唯尔有限公司。保留所有权利。
Background: Apigenin, a common edible plant flavonoid, is a well characterised antioxidant. The adipokine leptin exerts proliferative and anti-apoptotic activities in a variety of cell types. In cancer cells, apigenin may induce a pro-apoptotic pathway whereas leptin has an anti-apoptotic role. The purpose of the study is to investigate the role of apigenin and of leptin/leptin receptor pathway on proliferation and on apoptosis in lung adenocarcinoma.Methods: Immunocytochemistry, flow cytometry and RT-q-RT PCR, were used to investigate the expression and modulation of leptin receptors on the lung adenocarcinoma cell line A549 in presence or absence of apigenin and of leptin, alone or combined. Clonogenic test to evaluate cell proliferation was assessed. Exogenous leptin binding to its receptors by flow cytometry, reactive oxygen species (ROS) by dichlorofluorescein diacetate analysis, cell death by ethidium bromide and apoptosis by annexin V analysis were assessed. Apoptosis was assessed also in presence of lung adenocarcinoma pleural fluids (PF) (n = 6).Results: A549 express leptin/leptin receptor pathway and its expression is upregulated by apigenin. Apigenin alone or combined with leptin significantly decreases cell proliferation and significantly increases the spontaneous release of ROS, with augmented cell death and apoptosis, this latter also in the presence of lung adenocarcinoma PF. Leptin alone significantly increases cell proliferation and significantly decreases cell death.Conclusions: These results strongly suggest the potential utility of the flavonoid apigenin in the complementary therapeutic approach of patients with lung adenocarcinoma. (C) 2011 Elsevier Ltd. All rights reserved.