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核糖体蛋白 L5 介导的 c-Myc 抑制在桑根酮 G 诱导非小细胞肺癌细胞凋亡中起关键作用。

Ribosomal protein L5 mediated inhibition of c-Myc is critically involved in sanggenon G induced apoptosis in non-small lung cancer cells.

机构信息

College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

出版信息

Phytother Res. 2021 Feb;35(2):1080-1088. doi: 10.1002/ptr.6878. Epub 2020 Sep 16.

DOI:10.1002/ptr.6878
PMID:32935429
Abstract

Though Sanggenon G (SanG) from root bark of Morus alba was known to exhibit anti-oxidant and anti-depressant effects, its underlying mechanisms still remain unclear. Herein SanG reduced the viability of A549 and H1299 non-small lung cancer cells (NSCLCs). Also, SanG increased sub-G1 population via inhibition of cyclin D1, cyclin E, CDK2, CDK4 and Bcl-2, cleavages of poly (ADP-ribose) polymerase (PARP) and caspase-3 in A549 and H1299 cells. Of note, SanG effectively inhibited c-Myc expression by activating ribosomal protein L5 (RPL5) and reducing c-Myc stability even in the presence of cycloheximide and 20% serum in A549 cells. Furthermore, SanG enhanced the apoptotic effect with doxorubicin in A549 cells. Taken together, our results for the first time provide novel evidence that SanG suppresses proliferation and induces apoptosis via caspase-3 activation and RPL5 mediated inhibition of c-Myc with combinational potential with doxorubicin.

摘要

桑根酮 G(SanG)是从桑白皮中提取的一种化合物,已知具有抗氧化和抗抑郁作用,但具体作用机制尚不清楚。本研究表明,桑根酮 G 可降低非小细胞肺癌 A549 和 H1299 细胞的活力。此外,桑根酮 G 通过抑制细胞周期蛋白 D1、E、CDK2、CDK4 和 Bcl-2,诱导 A549 和 H1299 细胞的亚 G1 期细胞群增加,同时还能切割多聚(ADP-核糖)聚合酶(PARP)和 caspase-3。值得注意的是,桑根酮 G 通过激活核糖体蛋白 L5(RPL5)和降低 c-Myc 稳定性,即使在 A549 细胞中存在环己酰亚胺和 20%的血清,也能有效抑制 c-Myc 的表达。此外,桑根酮 G 可增强阿霉素在 A549 细胞中的凋亡作用。总之,我们的研究结果首次提供了新的证据,表明桑根酮 G 通过 caspase-3 激活和 RPL5 介导的 c-Myc 抑制,抑制细胞增殖并诱导细胞凋亡,与阿霉素具有联合作用潜力。

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