Jaceosidin induces apoptosis in ras-transformed human breast epithelial cells through generation of reactive oxygen species
Jaceosidin induces apoptosis in ras-transformed human breast epithelial cells through generation of reactive oxygen species
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DOI：
10.1196/annals.1397.052
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发表时间：
2007-01-01
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影响因子：
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通讯作者：
Surh, Young-Joon
中科院分区：
文献类型：
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作者：
Kim, Min-Jung;Kim, Do-Hee;Surh, Young-Joon
蒿属植物提取物具有抗炎和抗氧化活性。5，7-二羟基-3‘，4’，6-三甲氧基苯那酮(5，7-二羟基-3‘，4’，6-三甲氧基苯那酮)是一种从亚洲蒿属植物中提取的具有药理活性的黄酮类化合物，它能抑制佛波酯诱导的小鼠皮肤环氧合酶-2的表达和核因子-kappaB的激活，并能诱导ras转化的人乳腺上皮细胞(MCF10A-ras)细胞周期停滞。本文研究了从艾蒿中分离得到的菊花苷(4‘，5，7-三羟基-3’，6-二甲氧基黄酮)对MCF10A-ras细胞增殖的抑制作用。Jaceosidin对MCF10A-ras细胞存活率的抑制作用大于eupatilin。Jaceosidin处理导致MCF10A-ras细胞内ROS积累增加，这一作用可被抗氧化剂N-乙酰半胱氨酸(NAC)阻断。NAC可减弱Jaceosidin诱导的细胞毒性。为了更好地评估Jaceosidin的促凋亡作用，我们用流式细胞仪分析了处理后的细胞。100 mU组MCF10A-ras细胞亚二倍体或凋亡细胞比例增加(48.72%，对照组为7.78%)。Jaceosidin还可增加促凋亡Bax与抗凋亡Bax的比值，诱导caspase-3和多聚ADP-核糖聚合酶(PARP)的裂解。此外，Jaceosidin还上调了p53和p21的表达，而该化合物抑制了细胞生存信号的重要组成部分ERK1/2的激活。
Extracts of Artemisia plants possess anti-inflammatory and antioxidative activities. Eupatilin (5,7-dihydroxy-3',4',6-tri-methoxynavone), a pharmacologically active flavone derived from Artemisia asiatica, was shown to inhibit phorbol ester-induced cyclooxygenase-2 expression and NF-kappa B activation in mouse skin, and also to induce cell cycle arrest in ras-transformed human mammary epithelial (MCF10A-ras) cells. In this article, we examined the ability of jaceosidin (4',5,7-trihydroxy-3',6-dimethoxyflavone) isolated from Artemisia argyi to inhibit the proliferation of MCF10A-ras cells. Jaceosidin reduced the viability of MCF10A-ras cells to a greater extent than eupatilin. Jaceosidin treatment resulted in increased intracellular accumulation of reactive oxygen species (ROS) in MCF10A-ras cells, which was blocked by the antioxidant N-acetylcysteine (NAC). NAC attenuated jaceosidin-induced cytotoxicity. To better assess the proapoptotic effects of jaceosidin, we analyzed the treated cells by the flow cytometry. MCF10A-ras cells treated with jaceosidin (100 mu M) exhibited the increased proportion of hypodiploid or apoptotic cells (48.72% as composed to 7.78% in control cells). Jaceosidin treatment also increased the ratio of proapoptotic Bax to the antiapoptotic Bcl-2 and induced the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP). Moreover, jaceosidin elevated the expression of p53 and p21, while the compound inhibited the activation of ERK1/2 that is an important component of cell survival signaling.