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Supplementary Table 7 from Sophoridine Inhibits Human Colorectal Cancer Progression via Targeting MAPKAPK2

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posted on 2023-04-03, 16:44 authored by Rui Wang, Hongwei Liu, Yingying Shao, Kailong Wang, Shuangshuang Yin, Yuling Qiu, Honghua Wu, Erwei Liu, Tao Wang, Xiumei Gao, Haiyang Yu

Cancer-associated genes were retrieved from the disGeNET database

Funding

National Natural Science Foundation of China

Ministry of Science and Technology of China

Natural Science Foundation of Tianjin City

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ARTICLE ABSTRACT

Radian Sophorae flavescentis is a traditional Chinese medicine commonly used to treat cancer in China. However, its active components and underlying mechanism remain ambiguous. In this study, we have screened the pharmacokinetic parameters of the main chemical constituents of Radian Sophorae flavescentis by Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform and have found that Sophoridine is one of the best antitumor active ingredients. We have found that MAPKAPK2 is a potential target for Sophoridine by the PharmMapper and KEGG databXase analysis. Moreover, we have found that Sophoridine selectively inactivates phospho-MAPKAPK2 (Thr222) and directly binds into the ATP site of MAPKAPK2 by molecular docking. Furthermore, we have found out a direct binding between MAPKAPK2 and Sophoridine by cellular thermal shift assay and drug affinity responsive targets stability assay. The inhibition effects are further confirmed by Western blot: Sophoridine significantly decreases phospho-MAPKAPK2 (Thr222) in a time-dependent manner, but there is no obvious change in its total expression in colorectal cancer cells. Clinical studies have shown that a higher level of MAPKAPK2 is associated with a poorer percent survival rate (prognosis). Furthermore, a higher level of MAPKAPK2 is positively associated with the enrichment of downregulation of apoptosis and autophagy by gene set enrichment analysis, as well as upregulation of proliferation and cell-cycle arrest. Taken together, our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers. These studies show that Sophoridine may be a promising therapeutic strategy that blocks tumorigenesis in colorectal cancers.

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