Skip to main content
Figure 8 | BMC Cancer

Figure 8

From: Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

Figure 8

Schematic diagram showing possible mechanisms by which resveratrol (RSV) alters colon cancer cell kinetics. Obesity enhances insulin levels, which in turn elevates "bioactive IGF-1" levels by suppressing inhibitory IGF binding proteins (IGFBPs)-1 and -2. Activated IGF-1R phosphorylates a cascade of kinases PI3K, Akt and GSK3β. Phosphorylated and inactive GSK3β fails to form Axin/adenomatous polyposis coli (APC)/casein kinase 1 (CK1)/GSK3β destruction complex resulting in stabilization of cytosolic β-catenin and its subsequent nuclear translocation [reviewed in [64]]. In the nucleus, β-catenin binds to T-cell-factor 4 (TCF4) and stimulates the transcription of proliferative (e.g., cyclin D1) genes. The tumor suppressor p53, suppresses IGF-1R gene expression and phosphorylation. P53 attenuates IGF-1R transcription through its suppression of sp1, a critical mediator of IGF-1R transcription. Unphosphorylated, active FKHRL1 activates downstream target p27 and thus inhibiting cyclin D1 levels essential for cell cycle progression from G1 to S phase. Overall resveratrol suppresses IGF-1 induced colon cancer cell proliferation by A) downregulating IGF-1R levels, B) suppressing downstream IGF-1R/Akt and Wnt/β-catenin signaling C) activating p53 tumor suppressor protein, and by D) activation of FKHRL1/p27 signaling pathways.

Back to article page