AFPep
From Wikipedia, the free encyclopedia
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| Names | |
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| IUPAC name
Cyclo[L-asparaginyl-L-α-glutamyl-L-lysyl-L-threonyl-(4R)-4-hydroxy-L-prolyl-L-valyl-L-asparaginyl-(4R)-4-hydroxy-L-prolylglycyl] | |
| Other names
cyclo(EKTOVNOGN); alpha fetoprotein peptide; AFP peptide | |
| Identifiers | |
3D model (JSmol) |
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| Properties | |
| C40H64N12O16 | |
| Molar mass | 969.020 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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AFPep (alpha fetoprotein peptide) is an orally-active, cyclic, 9-amino acid, peptide with a molecular weight of 969 daltons and is derived from the anti-oncogenic active site (residues 472–479) of alpha fetoprotein (AFP).[1] Using the standard amino acid abbreviations, AFPep has the sequence cyclo(EKTOVNOGN), where O is hydroxyproline. This peptide has been shown in experimental animal models to be efficacious in the prevention and treatment of ER+ breast cancer.[2]
Background
Multiple births by a woman are strongly associated with a lower risk of developing breast cancer later in her life.[3] One of the contributing factors for this association appears to be the alpha fetoprotein (AFP) produced by the fetal liver, which crosses the placenta and enters into the maternal circulation.[4] Pregnancy-associated protection from breast cancer is directly proportional to level of exposure to AFP.[5] Furthermore, it has been demonstrated that tumor growth can be inhibited by AFP in animal models of breast cancer.[6][7] It is speculated that AFP may induce apoptosis in pre-malignant breast tissue cells which would have later developed into malignancies.[3]
Anti cancer effects
Through mimicking the effects of AFP, AFPep inhibits the proliferation of estrogen receptor-positive human breast cancer cells growing in culture.[8] It is also able to inhibit the estrogen stimulated growth of human breast cancer cells growing as xenografts in immunodeficient mice.[8] According to a recent study, AFPep prevents the development of carcinogen-induced breast cancer in an animal model.[9] Hence AFPep may have utility for preventing or treating estrogen receptor-positive breast cancer.
Mechanism of action
AFPep inhibits estrogen-stimulated growth of immature mouse uterus and thus is antiestrogenic.[1] In culture, AFPep inhibits the estrogen induced proliferation of T47D cells but has no effect on the basal growth.[10] AFPep also inhibits phosphorylation of the estrogen receptor and activates the phosphorylation of p53.[10]
AFPep has been shown to bind the heat shock protein Hsp72.[11] Hsp72 together with Hsp90 form a heterocomplex with the estrogen receptor. Hence AFPep through interaction with Hsp72 controls the ligand binding and transcriptional activation of the estrogen receptor.