Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Curcumin has demonstrated inhibitory effects on urothelial tumor development in preclinical models.
• Aberrant activation of Insulin-like Growth Factor 2 (IGF2) signaling is implicated in various cancers, including bladder cancer.

Purpose of the Study:

• To elucidate the molecular mechanisms by which curcumin inhibits urothelial tumor development.
• To investigate the role of IGF2 and the PI3K/AKT/mTOR signaling pathway in curcumin's anti-tumor effects.

Main Methods:

• Investigated curcumin's effect on IGF2 expression at the transcriptional level.
• Assessed phosphorylation levels of key proteins in the IGF1R/IRS-1 and AKT/mTOR pathways in bladder cancer cells and tumor tissues.
• Utilized ectopic expression of IGF2 and IGF1R, and constitutively active AKT1 to validate targets and pathways.

Main Results:

• Curcumin significantly inhibits IGF2 expression and downstream IGF2-mediated PI3K/AKT/mTOR signaling.
• Curcumin decreases phosphorylation of IGF1R and IRS-1, key components of the IGF signaling cascade.
• Restoration of IGF2 or IGF1R expression, or activation of AKT1, counteracted curcumin's inhibitory effects on cell proliferation and migration.

Conclusions:

• Curcumin suppresses urothelial tumor development by targeting IGF2 and inhibiting the IGF2-mediated PI3K/AKT/mTOR signaling pathway.
• These findings highlight IGF2 as a crucial mediator of curcumin's action and suggest a potential therapeutic strategy for bladder cancer involving IGF2 targeting.