Fenretinide (4-HPR): A Preventive Chance for Women at Genetic and Familial Risk?
Table 1
Mechanism of action of Fenretinide (4-HPR). Corresponding references: [16–29].
Mechanism of action
Effect
Receptor dependent
RAR-α, β, γ and RXR-α, β, γ (ligand-activated transcription factors)
Regulation of growth, differentiation, and apoptosis
Receptor independent
Generation of ROS: hydrogen peroxide and superoxide Induction of COX-2 expression by HER2/neu through activation of Akt Production of nitric oxide by NOS in BRCA 1 mutated breast cancer cells C-erbB-2 protein and mRNA downregulation Sphingolipid ceramide elevation and membrane synthesis alterations Mitochondrial damage with cytochrome-C release, disruption of mitochondrial transmembrane potential, and ROS generation Caspases activation
Apoptosis
Induction of growth inhibition factors Inhibition of growth stimulating factors (IGF-1) Increased secretion of IGFBPs TGF-β secretion
Cell growth inhibition
Decreased telomerase activity in MNU-induced mammary tumor and bronchial epithelium of cigarette smokers
