In vitro (cell line) · PMID 41891524
Vasoactive Intestinal Peptide Induces Autophagy and Cytotoxicity in Renal Cell Carcinoma via SIRT3-Dependent Signaling Pathway — VialBase Research
VIP (0-50 microM) exhibits dose-dependent cytotoxicity in VPAC1-expressing RCC cells
Last updated · 2026 · Li L, Wang D, Zhang J, Xiao F, Shao C · Journal of Biochemical and Molecular Toxicology
Key findings
- VIP (0-50 microM) exhibits dose-dependent cytotoxicity in VPAC1-expressing RCC cells
- Reduced cell viability, increased LDH and gamma-GPT release
- Induced oxidative stress (elevated ROS, MDA; decreased SOD2)
- At 5-10 microM: induced autophagy (increased LC3-II/LC3-I, Beclin1, p62 degradation)
- Mechanism: SIRT3 downregulation -> increased Ac-FOXO1
- SIRT3 overexpression counteracted VIP-induced autophagy
PMID 41891524 — VIP in Renal Cell Carcinoma
Compound: VIP Citation: Li L et al. J Biochem Mol Toxicol. 2026;40(4):e70815. doi:10.1002/jbt.70815
Summary
Investigated VIP’s effects on VPAC1-expressing renal cell carcinoma (RCC) Caki-1 cells. Discovered dose-dependent cytotoxicity and autophagy induction via SIRT3/FOXO1 pathway.
Key Findings
- Cytotoxicity: Dose-dependent (0-50 microM) reduction in cell viability
- Oxidative stress: Elevated ROS and MDA, decreased SOD2
- Autophagy induction: At 5-10 microM — increased LC3-II/LC3-I ratio, upregulated Beclin1, accelerated p62 degradation
- Mechanism: SIRT3 downregulation -> FOXO1 acetylation -> autophagy activation
- Rescue: SIRT3 overexpression counteracted VIP-induced autophagy
Significance
Reveals an unexpected anti-cancer property of VIP in VPAC1-expressing cancers. This contrasts with VIP’s typically protective/anti-inflammatory role and suggests context-dependent effects. Relevant for understanding VIP’s complex biology beyond immunomodulation.
See Also
- Parent compound: VIP