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Lotus (Nelumbo nucifera) seedpod extract inhibits cell proliferation and induces apoptosis in non‐small cell lung cancer cells via downregulation of Axl
Journal of Food Biochemistry ( IF 3.5 ) Pub Date : 2020-12-31 , DOI: 10.1111/jfbc.13601
Nam-Yi Kim 1 , In-Jun Yang 2 , Soyoung Kim 1 , ChuHee Lee 3
Affiliation  

Non‐small‐cell lung cancer (NSCLC) is the most frequent cause of cancer‐related death. In this study, we found the anticancer activity of lotus seedpod extract (LSPE) in NSCLC cells, since LSPE treatment inhibited cell proliferation of A549 and H460 cells in a dose‐dependent manner and the clonogenic activities of LSPE‐treated cells were also reduced. In LSPE‐treated cells, the cleavage of poly (ADP‐ribose) polymerase (PARP) and phosphorylation of H2X, were also observed, indicating the pro‐apoptotic effect of LSPE. Next, we found that LPSE treatment diminished the levels of protein and mRNA of Axl, a receptor tyrosine kinase (RTK) that transduces critical signals for cell proliferation and inhibition of apoptosis. The promoter activity of Axl was found to be dose‐dependently decreased in response to LSPE treatment, implying that LSPE inhibited Axl gene expression at transcriptional level. In addition, Axl overexpression was found to decrease the effects of LSPE on inhibition of cell proliferation and colony formation as well as induction of PARP cleavage and phosphorylation of H2AX, while the same activities of LPSE were increased by knockdown of Axl gene expression, indicating that the antiproliferative and pro‐apoptotic effect of LSPE is inversely proportional to the protein level of Axl. Taken together, we found that the LSPE suppressed cell proliferation and induced apoptosis of NSCLC cells, which is attenuated or augmented by overexpression or RNA interference of Axl expression, respectively. Our data suggest that Axl is a novel therapeutic target of LSPE to inhibit cell proliferation and promote apoptosis in NSCLC cells.

中文翻译:

莲子(Nelumbo nucifera)种荚提取物通过下调Axl抑制非小细胞肺癌细胞的增殖并诱导其凋亡

非小细胞肺癌(NSCLC)是癌症相关死亡的最常见原因。在这项研究中,我们发现莲子荚提取物(LSPE)在NSCLC细胞中具有抗癌活性,因为LSPE处理以剂量依赖性方式抑制A549和H460细胞的细胞增殖,并且LSPE处理的细胞的克隆形成活性也降低了。在LSPE处理过的细胞中,还观察到了聚(ADP-核糖)聚合酶(PARP)的裂解和H2X的磷酸化,表明LSPE具有促凋亡作用。接下来,我们发现LPSE处理可降低Axl的蛋白质和mRNA水平,Axl是一种受体酪氨酸激酶(RTK),可转导细胞增殖和凋亡抑制的关键信号。Axl的启动子活性被发现对LSPE治疗有剂量依赖性的降低,这表明LSPE在转录水平上抑制了Axl基因的表达。此外,发现Axl的过表达降低了LSPE对细胞增殖和集落形成的抑制作用以及PARP裂解和H2AX磷酸化的诱导作用,而敲除Axl基因表达则增加了LPSE的相同活性,表明LSPE的抗增殖和促凋亡作用与Axl的蛋白质水平成反比。综上所述,我们发现LSPE抑制了NSCLC细胞的增殖并诱导了NSCLC细胞的凋亡,其被Axl的过表达或RNA干扰减弱或增强。表达式。我们的数据表明,Axl是LSPE的新型治疗靶标,可抑制细胞增殖并促进NSCLC细胞凋亡。
更新日期:2021-02-22
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