Ribosomal proteinL5mediated inhibition ofc-Mycis critically involved in sanggenon G induced apoptosis in non-small lung cancer cells
Ribosomal proteinL5mediated inhibition ofc-Mycis critically involved in sanggenon G induced apoptosis in non-small lung cancer cells
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DOI：
10.1002/ptr.6878
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发表时间：
2020-09-16
影响因子：
7.2
通讯作者：
Kim，Sung-Hoon
中科院分区：
文献类型：
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作者：
Park，Ji Eon;Jung，Ji Hoon;Kim，Sung-Hoon
桑根皮中的桑根酮G（Sanggenon G，SanG）具有抗氧化和抗衰老作用，但其作用机制尚不清楚。本文中，SanG降低了A549和H1299非小细胞肺癌细胞（NSCLC）的活力。此外，SanG通过抑制A549和H1299细胞中的细胞周期蛋白D1、细胞周期蛋白E、CDK 2、CDK 4和Bcl-2、多聚腺苷二磷酸核糖聚合酶（PARP）和半胱天冬酶-3的裂解来增加亚G1群体。值得注意的是，即使在放线菌酮和20%血清存在的情况下，SanG也能通过激活核糖体蛋白L5（RPL 5）并降低c-Myc稳定性来有效抑制c-Myc表达。此外，SanG增强阿霉素对A549细胞的凋亡作用。总之，我们的结果首次提供了新的证据，即SanG通过caspase-3激活和RPL 5介导的c-Myc抑制作用抑制增殖并诱导凋亡，并具有与多柔比星结合的潜力。
Though Sanggenon G (SanG) from root bark ofMorus albawas 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.