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Citronellol potentiates sunitinib efficacy in renal cell carcinoma by targeting JAK2/STAT3 signaling pathway

Zongrun Sun1, Zixuan Chen1, Yuesong Cai2

  • 1Department of Urology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, No.1111 Xian Xia Road, Shanghai, 200336, China.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|March 5, 2026
PubMed

Insights

Citronellol enhances sunitinib efficacy in renal cell carcinoma (RCC) by overcoming drug resistance. This plant compound targets key signaling pathways, offering a promising new strategy for kidney cancer treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Renal cell carcinoma (RCC) is the most common kidney cancer.
  • Resistance to tyrosine kinase inhibitors (TKIs) like sunitinib limits RCC treatment effectiveness.

Purpose of the Study:

  • To investigate Citronellol's potential to enhance sunitinib sensitivity in RCC.
  • To elucidate the molecular mechanisms underlying Citronellol's effects on RCC.

Main Methods:

  • Network pharmacology analysis to identify Citronellol targets.
  • In vitro experiments using RCC cell lines (786-O and A498).
  • Western blot analysis to assess signaling pathway modulation.

Main Results:

  • Citronellol inhibited RCC cell proliferation, migration, and induced apoptosis.
  • Citronellol significantly reduced sunitinib's IC50 value and enhanced its anti-cancer effects.
  • Citronellol suppressed EGFR, JAK2, and STAT3 phosphorylation.

Conclusions:

  • Citronellol enhances sunitinib efficacy in RCC by inhibiting the JAK2/STAT3 signaling pathway.
  • This combination strategy shows promise for overcoming TKI resistance in kidney cancer.
  • Citronellol represents a potential therapeutic agent for improving RCC treatment outcomes.
Keywords:
CitronellolJAK2/STAT3 signaling pathwaysNetwork pharmacologyRenal Cell CarcinomaSunitinib

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