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Curcumin Negatively Regulates Cigarette Smoke-Induced Renal Cell Carcinoma Epithelial-Mesenchymal Transition Through

Tao Zhang1, Li Zhao2, Taotao Zhang1

  • 1Department of Urologic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, People's Republic of China.

Oncotargets and Therapy
|October 16, 2020
PubMed
Abstract

Insights

Cigarette smoke promotes renal cell carcinoma (RCC) by activating the ERK5/AP-1 pathway, driving epithelial-mesenchymal transition (EMT). Curcumin and XMD8-92 inhibit this process, offering potential therapeutic strategies for smoking-associated kidney cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Renal cell carcinoma (RCC) development mechanisms at the molecular level are under-researched.
  • Epithelial-mesenchymal transition (EMT) is crucial in tumor genesis and progression, often involving mitogen-activated protein kinase (MAPK) pathways.
  • This study investigates the role of the ERK5/AP-1 pathway in EMT-driven RCC progression.

Purpose of the Study:

  • To elucidate the molecular mechanisms linking cigarette smoke exposure to renal cell carcinoma (RCC) progression.
  • To investigate the role of epithelial-mesenchymal transition (EMT) and the ERK5/AP-1 pathway in cigarette smoke-induced RCC.
  • To evaluate the potential of curcumin as an intervention for smoking-associated RCC.

Main Methods:

  • Utilized RCC cell lines exposed to cigarette smoke extract (CSE) in vitro.
  • Employed immunohistochemistry (IHC), Western blotting, and real-time quantitative reverse transcription PCR.
  • Assessed EMT by analyzing cell morphology, invasion, migration, and epithelial/mesenchymal marker expression.

Main Results:

  • Down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, and TWIST in smoking-associated RCC tissues.
  • Cigarette smoke extract (CSE) activates the ERK5/AP-1 pathway, promoting RCC EMT.
  • ERK5 inhibition (XMD8-92) or curcumin treatment reversed CSE-induced EMT by inhibiting the ERK5/AP-1 pathway.

Conclusions:

  • The ERK5/AP-1 signaling pathway is vital in cigarette smoke-associated RCC development.
  • Inhibition of the ERK5/AP-1 pathway represents a potential therapeutic strategy for smoking-related kidney cancer.
  • Curcumin demonstrates efficacy in reversing CSE-induced EMT via the ERK5/AP-1 pathway.
Keywords:
ERK5/AP-1 pathwaycigarette smokecurcuminepithelial–mesenchymal transitionrenal cell carcinoma

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