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A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine

Un-Jung Yun1, Su-Jin Bae1, Yu-Rim Song1

  • 1School of Korean Medicine, Dongguk University, Gyeongju 38066, Korea.

International Journal of Molecular Sciences
|February 15, 2022
PubMed

Insights

Evodiamine effectively inhibits liver cancer growth by targeting the Yes-associated protein (YAP) pathway. This natural compound reduces YAP levels, induces cancer cell death, and inhibits metastasis, offering a potential new therapy for advanced hepatocellular carcinoma (HCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) often presents with advanced symptoms, and current treatments like sorafenib face resistance.
  • The Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) pathway is implicated in various cancer progressions, including metastasis.
  • YAP is frequently overexpressed in patient-derived HCC tissues, suggesting its role in liver cancer development.

Purpose of the Study:

  • To investigate the potential of evodiamine, a known anticancer agent, in inhibiting YAP.
  • To determine if evodiamine can modulate hepatocellular carcinoma (HCC) progression by targeting YAP.
  • To explore the therapeutic potential of evodiamine as a novel treatment for advanced HCC.

Main Methods:

  • Analysis of YAP overexpression in patient-derived HCC tissues.
  • Dose-dependent evaluation of evodiamine's effect on HCC cell growth and YAP levels.
  • Biochemical assays to identify mechanisms of cell death, including mitochondrial dysfunction and apoptosis.
  • Assessment of evodiamine's impact on HCC cell migration and invasion, and vimentin expression.

Main Results:

  • Evodiamine significantly reduced HCC cell growth and YAP levels in a dose-dependent manner.
  • Mitochondrial dysfunction-mediated apoptosis was identified as the mechanism behind evodiamine's cytotoxic effect.
  • YAP was found to be overexpressed in metastatic HCC tissues compared to primary tumors.
  • Evodiamine demonstrated anti-metastatic properties by inhibiting migration and invasion and reducing vimentin levels in HCC cells.

Conclusions:

  • YAP is a critical therapeutic target for hepatocellular carcinoma (HCC).
  • Evodiamine exhibits significant anticancer and anti-metastatic effects in HCC by downregulating YAP.
  • Evodiamine represents a promising candidate for developing novel, targeted therapies for advanced HCC.
Keywords:
AMPKHCCYAPevodiamineliver cancer

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