Erianthridin 通过抑制细胞外信号调节激酶活性诱导非小细胞肺癌细胞凋亡,Planta Medica

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Erianthridin 通过抑制细胞外信号调节激酶活性诱导非小细胞肺癌细胞凋亡
Planta Medica ( IF 2.1 ) Pub Date : 2020-11-19 , DOI: 10.1055/a-1295-8606
Sirima Boonjing ₁ , Sutthaorn Pothongsrisit ₁ , Onsurang Wattanathamsan ₂ , Boonchoo Sritularak ₃ , Varisa Pongrakhananon _{1,

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Affiliation

由于肺癌的高死亡率，天然衍生化合物已被推广为抗癌药物发现的通用来源。Erianthridin 是一种从 Dendrobium formosum 中分离的菲化合物，在非小细胞肺癌细胞中表现出有趣的凋亡诱导作用。凋亡细胞核染色分析表明，凋亡细胞有明显的 DNA 断裂和凋亡小体，并且在用毛菊素处理的细胞中发现膜联蛋白 V-FITC 阳性细胞增加。切割的 caspase-3 和切割的聚 ADP 核糖聚合酶的凋亡蛋白标记物响应毛菊素显着上调。一项机制研究表明，毛菊素能够减弱细胞外信号调节的激酶活性，从而通过调节 Bcl-2 家族蛋白水平来介导细胞凋亡。U0126，一种细胞外信号调节激酶抑制剂，增强了毛菊素的凋亡诱导作用；相比之下，外源性细胞外信号调节激酶的过度表达基本上消除了毛菊素的活性。此外，体外 3D 肿瘤发生分析表明，毛菊素能够潜在地抑制肺癌细胞增殖。本研究首次报道了毛菊素具有良好的细胞毒作用，为进一步研究和开发该化合物提供了临床前证据。增强毛蕊花素的凋亡诱导作用；相比之下，外源性细胞外信号调节激酶的过度表达基本上消除了毛菊素的活性。此外，体外 3D 肿瘤发生分析表明，毛菊素能够潜在地抑制肺癌细胞增殖。本研究首次报道了毛菊素具有良好的细胞毒作用，为进一步研究和开发该化合物提供了临床前证据。增强毛蕊花素诱导细胞凋亡的作用；相比之下，外源性细胞外信号调节激酶的过度表达基本上消除了毛菊素的活性。此外，体外 3D 肿瘤发生分析表明，毛菊素能够潜在地抑制肺癌细胞增殖。本研究首次报道了毛菊素具有良好的细胞毒作用，为进一步研究和开发该化合物提供了临床前证据。

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Erianthridin Induces Non-small Cell Lung Cancer Cell Apoptosis through the Suppression of Extracellular Signal-regulated Kinase Activity

Due to the high mortality of lung cancer, natural derivative compounds have been promoted as versatile sources for anticancer drug discovery. Erianthridin, a phenanthrene compound isolated from Dendrobium formosum, exhibits intriguing apoptosis-inducing effects in non-small cell lung cancer cells. Apoptotic nuclei staining assays showed that apoptotic cells with DNA fragmentation and apoptotic bodies were apparent, and an increase in annexin V-FITC-positive cells were found in cells treated with erianthridin. The apoptosis protein markers for cleaved caspase-3 and cleaved poly-ADP-ribose polymerase were significantly upregulated in response to erianthridin. A mechanistic investigation revealed that erianthridin was able to attenuate extracellular signal-regulated kinase activity and thereby mediate apoptosis through the modulation of Bcl-2 family protein levels. U0126, an extracellular signal-regulated kinase inhibitor, augmented the apoptosis-inducing effect of erianthridin; in contrast, overexpression of exogenous extracellular signal-regulated kinase substantially abrogated erianthridin activity. Furthermore, an in vitro 3D tumorigenesis assay showed that erianthridin was able to potentially suppress lung cancer cell proliferation. This study is the first to report a promising cytotoxic effect of erianthridin, which provides preclinical evidence for further research and development of this compound.

更新日期：2020-11-19

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