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

• Published in: Phytotherapy research Vol. 35; no. 2; pp. 1080 - 1088
• Main Authors: Park, Ji Eon, Jung, Ji Hoon, Lee, Hyo‐Jung, Sim, Deok Yong, Im, Eunji, Park, Woon Yi, Shim, Bum Sang, Ko, Seong‐Gyu, Kim, Sung‐Hoon
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.2021; Wiley Subscription Services, Inc
• Subjects: A549; Adenosine diphosphate; Apoptosis; Bark; Benzofurans - chemistry; Carcinoma, Non-Small-Cell Lung - genetics; Caspase; Cell Line, Tumor; Chromones - chemistry; Cyclin D1; Cyclin E; Cyclin-dependent kinase 2; Cyclin-dependent kinase 4; Cycloheximide; c‐Myc; Doxorubicin; Genes, myc - genetics; Humans; Lung cancer; Lung Neoplasms - genetics; Myc protein; Oxidants; Oxidizing agents; Poly(ADP-ribose) polymerase; Proteins; Ribose; Ribosomal Proteins - metabolism; RPL5; SanG; Transfection; SanG; RPL5; apoptosis; c-Myc; A549
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6878

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.