奶油
癌症研究
下调和上调
细胞凋亡
结直肠癌
信号转导
蛋白激酶B
安普克
化学
磷酸化
癌症
细胞生物学
内科学
生物
医学
蛋白激酶A
转录因子
生物化学
基因
作者
Si‐Yang Li,Jin Shang,Xiao‐Mei Mao,Rui Fan,Huiqi Li,Ruihan Li,Dong‐Yan Shen
标识
DOI:10.1016/j.ejphar.2021.174370
摘要
Colorectal cancer (CRC) is the most fatal gastrointestinal tumor and it is urge to explore powerful drugs for the treatment. Diosgenin (DSG) as a new steroidal had been reported exerts anti-tumor activity in multiple cancers, including CRC. However, the potential mechanism of DSG suppresses CRC remains further to be revealed. Here, we reported that DSG inhibited proliferation of CRC cells in dose- and time-dependent manner, induced apoptosis by modulating p53 and Bcl-2 family proteins expression to mediate mitochondrial apoptosis pathway, suppressed migration and invasion by reducing MMP-9 (matrix metalloproteinase) and decreased aerobic glycolysis by mediating glucose transporter (GLUT) like GLUT3 and GLUT4, and pyruvate carboxylase PC downregulation. Intriguingly, mechanistic study suggests those phenotypes involved DSG inhibited cAMP/PKA/CREB pathway in CRC cells, and result to inhibit the phosphorylation of CREB to regulate the transcription of genes above-mentioned. Finally, nude mice xenograft tumor model further indicated that DSG could be a great agent to suppress the growth of CRC cells in vivo and have no obvious side effects. Taken together, we revealed a unique mechanism that DSG suppresses CRC cells through cAMP/PKA/CREB pathway and DSG is a promising candidate drug for CRC treatment.
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