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6-Gingerol suppresses tumor cell metastasis by increasing YAPser127 phosphorylation in renal cell carcinoma

Shan Xu1,2,3, Haibao Zhang1,2,3, Tianjie Liu1,2,3

  • 1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Journal of Biochemical and Molecular Toxicology
|September 14, 2020
PubMed

Insights

6-Gingerol, a compound from ginger, effectively inhibits kidney cancer (renal cell carcinoma) cell migration and metastasis. It works by reducing key proteins and impacting YAP signaling, offering a potential natural therapy for kidney cancer treatment.

Area of Science:

  • Oncology
  • Natural Products Chemistry
  • Molecular Biology

Background:

  • Renal cell carcinoma (RCC) incidence and mortality are rising globally.
  • Current RCC treatments like immunotherapy and targeted therapy face challenges with side effects and resistance.
  • Natural products are being explored as adjunctive therapies for RCC due to potentially fewer side effects.

Purpose of the Study:

  • To investigate the anti-metastatic effects of 6-gingerol, a key component of ginger, on renal cell carcinoma (RCC).
  • To elucidate the underlying molecular mechanisms by which 6-gingerol inhibits RCC cell migration and metastasis.

Main Methods:

  • In vitro and in vivo studies using RCC cell lines (786-O, ACHN).
  • Western blot analysis to assess protein levels (MMP2, Slug, Vimentin, YAP).
  • Loss-of-function and gain-of-function experiments involving YAP.
  • Transwell assays to evaluate cell migration.
  • Immunofluorescence microscopy to observe F-actin and cell morphology.

Main Results:

  • 6-Gingerol significantly suppressed RCC cell migration and metastasis in vitro and in vivo.
  • Treatment with 6-gingerol reduced protein levels of MMP2, Slug, and Vimentin.
  • 6-Gingerol increased YAP phosphorylation at Ser127 and decreased nuclear YAP levels.
  • YAP was found to promote RCC cell migration, with its silencing downregulating MMP2, Slug, and Vimentin, and overexpression upregulating them.
  • 6-Gingerol's effect on YAP led to disordered F-actin and reduced lamellipodia, impairing cell migration.

Conclusions:

  • 6-Gingerol demonstrates significant potential as an antimetastatic agent for renal cell carcinoma (RCC).
  • The mechanism involves the modulation of the YAP signaling pathway, leading to reduced expression of MMP2, Slug, and Vimentin.
  • 6-Gingerol represents a promising natural compound for adjunctive therapy in kidney cancer treatment.
Keywords:
6-gingerolRCCYAPmigration

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