2. Academic Validation
  3. Corosolic acid inhibits cancer progression by decreasing the level of CDK19-mediated O-GlcNAcylation in liver cancer cells

Corosolic acid inhibits cancer progression by decreasing the level of CDK19-mediated O-GlcNAcylation in liver cancer cells

  • Cell Death Dis. 2021 Sep 29;12(10):889. doi: 10.1038/s41419-021-04164-y.
Congcong Zhang 1 2 3,  Yongjie Niu 1 2,  Zhixian Wang 1 2,  Xin Xu 1,  Yan Li 4,  Lifang Ma 5 6,  Jiayi Wang 7 8,  Yongchun Yu 9 10
Affiliations

Affiliations

  • 1 Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, P.R. China.
  • 2 Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 200071, Shanghai, P.R. China.
  • 3 Henan University of Chinese Medicine, 450046, Zhengzhou, P.R. China.
  • 4 Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 200071, Shanghai, P.R. China.
  • 5 Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, P.R. China. [email protected].
  • 6 Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, China. [email protected].
  • 7 Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, P.R. China. [email protected].
  • 8 Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, China. [email protected].
  • 9 Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, 200030, Shanghai, P.R. China. [email protected].
  • 10 Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 200071, Shanghai, P.R. China. [email protected].
PMID: 34588426 DOI: 10.1038/s41419-021-04164-y
Abstract

Diabetes is an important risk factor for liver Cancer, but its mechanism is unknown. Corosolic acid (CA) has been proven to have both hypoglycemic and antitumor effects, so revealing the function of CA can help us understand the relationship between diabetes and liver Cancer. In previous studies, we confirmed that CA can effectively inhibit the expression of YAP, an important oncoprotein in HCC cells, and the proliferation of HCC cells. In addition, we also found that O-GlcNAcylation plays an indispensable role in HCC tumorigenesis. However, it is not clear whether CA can inhibit the effect of O-GlcNAcylation on HCC cells. In this study, the antitumor ability of CA was investigated by inhibiting the O-GlcNAcylation level and its corresponding mechanism. The results showed that HG (high glucose) could promote the proliferation of liver Cancer cells, while CA could inhibit cell growth under HG conditions and tumor growth in a xenotransplantation model. CA can inhibit the activation of the HBP pathway and reduce the expression of YAP and OGT under HG conditions. Importantly, we found that CA can reduce YAP expression and O-GlcNAcylation by inhibiting the activity of CDK19. Overexpression of CDK19 partially reversed the CA-induced decrease in YAP and O-GlcNAcylation. This is the first evidence that CA can reduce the proliferative capacity of cells with high glucose levels and further inhibit tumor growth by inactivating the CDK19/YAP/O-GlcNAcylation pathway, suggesting that CA is a candidate drug for the development of treatments against diabetes-associated liver Cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101800
    99.72%, CDK8/19 Inhibitor
    CDK