Discovery of a novel dual-target inhibitor against RSK1 and MSK2 to suppress growth of human colon cancer

Guoguo Jin, Mingyang Yan, Kangdong Liu, Ke Yao, Hanyong Chen, Chengjuan Zhang, Yang Yi, Kanamata Reddy, Dhilli Rao Gorja, Kyle Vaughn Laster, Zhiping Guo, Zigang Dong

Research output: Contribution to journalArticlepeer-review


Colon cancer is the most aggressive tumor in both men and women globally. As many the chemotherapeutic regimens have adverse side effects and contribute to the resistance and recurrence, therefore, finding novel therapeutic targets and developing effective agents are urgent. Based on the TCGA and GTEx database analysis, RSK1 and MSK2 were found abnormal expressed in colon cancer. RSK1 and MSK2 were overexpressed in colon cancer tissues confirmed by western blot and IHC. After knocking down RSK1 or MSK2, cell proliferation and anchorage-independent cell growth were markedly inhibited. Using a computer docking model, we identified a novel dual-target inhibitor, APIO-EE-07, that could block both RSK1 and MSK2 kinase activity in a dose-dependent manner. APIO-EE-07 inhibited cell growth and induced apoptosis and also increased expression of Bax as well as cleaved caspase-3 and -PARP in colon cancer cells by downregulating RSK1 and MSK2 downstream targets, including CREB and ATF1. Furthermore, APIO-EE-07 decreased tumor volume and weight in human patient-derived xenografts tumors implanted in SCID mice. In summary, our results demonstrate that RSK1 and MSK2 are the potential targets for the treatment of colon cancer. APIO-EE-07, a novel dual-target inhibitor of RSK1 and MSK2, can suppress the growth of colon cancer by attenuating RSK1 and MSK2 signaling.

Original languageEnglish (US)
Pages (from-to)6733-6746
Number of pages14
Issue number43
StatePublished - Oct 22 2020

Bibliographical note

Funding Information:
Funding This work was supported by the Key Science and Technology Program of Henan Province, China (182102310125) and the Key program of TCM research in Henan Province, China (2018ZY1016, 2019ZY1037).

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


Dive into the research topics of 'Discovery of a novel dual-target inhibitor against RSK1 and MSK2 to suppress growth of human colon cancer'. Together they form a unique fingerprint.

Cite this