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Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1

Jiansong Wu1, Qiang Niu1, Jie Yuan1

  • 1Department of Infectious Diseases, General Hospital of the People's Liberation Army Rocket Force, Beijing 100088, P.R. China.

Experimental and Therapeutic Medicine
|November 29, 2019
PubMed

Insights

Phenazine biosynthesis-like domain-containing protein (PBLD) inhibits hepatocellular carcinoma (HCC) progression. Cedrelone, a PBLD activator, shows therapeutic potential for HCC by targeting PBLD, offering a new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Phenazine biosynthesis-like domain-containing protein (PBLD) expression is reduced in hepatocellular carcinoma (HCC).
  • The precise biological role of PBLD in HCC and agents that can upregulate it remain largely unknown.

Purpose of the Study:

  • To investigate the relationship between PBLD and HCC.
  • To evaluate the therapeutic efficacy of cedrelone in HCC by targeting PBLD.

Main Methods:

  • Analysis of clinicopathological HCC specimens.
  • Utilized a HCC cell model, microarray analysis, and an animal model.
  • Investigated the effects of cedrelone on PBLD overexpression and associated signaling pathways.

Main Results:

  • PBLD was found to inhibit HCC progression.
  • Cedrelone demonstrated therapeutic effects in HCC through PBLD overexpression.
  • Cedrelone suppressed epithelial-mesenchymal transition, reduced growth rate, and increased apoptosis in HCC cells with PBLD overexpression.
  • Cedrelone regulated Ras and Ras-proximate-1 signaling pathways via PBLD activation.

Conclusions:

  • PBLD serves as an independent predictor of HCC progression and a potential therapeutic target.
  • Cedrelone, as a PBLD activator, represents a promising therapeutic agent for future HCC treatment.
Keywords:
cedrelonehepatocellular carcinomaphenazine biosynthesis-like domain-containing protein

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