AFPep: an anti-breast cancer peptide that is orally active

Abstract

Chronic oral administration of AFPep appears to be safe and effective for the treatment or prevention of breast cancer in animal models.

An α-fetoprotein-derived peptide reduces the uterine hyperplasia and increases the antitumour effect of tamoxifen

“…Doses of AFPep (100 mg animal À1 day À1 ;) or of Tam (0.05 mg animal À1 day À1 ) given to the rats were held constant during the 20-day treatment interval. During this interval, all animals in all groups gained In all previous work with high doses of AFPep, no evidence of toxicity or side effects has been detected (Mesfin et al, 2001;Bennett et al, 2002Bennett et al, , 2006Parikh et al, 2005). In this study in which AFPep or combination of AFPep and Tam were administered to rats at therapeutic doses for 2 -3 weeks, there was no effect on body weight, fur texture, or cage activity during the lifespan of the animals, or on organ weights obtained at necropsy (Table 1).…”

“…Figure 1A In data not shown, it was apparent that, at concentrations ranging from 10 À8 to 10 À5 M, neither Tam nor AFPep inhibited the basal (no E 2 ) growth of T47D cells, suggesting that their action was directed mainly to the E 2 stimulation of these cells and was not a nonspecific toxic effect. Also, a control peptide of scrambled sequence did not inhibit the E 2 -stimulated or basal growth of these cells (Bennett et al, 2006) Although T47D cells were quite responsive to E 2 in cell culture, these cells were less reliable when grown as a xenograft in immune-deficient mice, having a take rate (i.e., successful growth) of o60% when implanted in 20 of these mice. In contrast, we have found the MCF-7 human breast cancer cell line to have a tumour take rate of 100% in immune-deficient mice and to be completely dependent on E 2 for growth in these mice.…”

“…Ten million MCF-7 human breast cancer cells were harvested from culture, centrifuged into a pellet, solidified into a fibrin clot, and implanted under the kidney capsule of SCID mice as described previously (Bennett et al, 1985(Bennett et al, , 2002(Bennett et al, , 2006Mesfin et al, 2001;Parikh et al, 2005). Oestrogen supplementation was accomplished by s.c. implantation of a 5 mm silastic tubing capsule containing solid E 2 inserted on the day of tumour implantation.…”

“…A peptide (a-fetoprotein-derived peptide (AFPep), sequence cyclo(EKTOVNOGN), where O is hydroxyproline) derived from the active site of a-fetoprotein (AFP) has been under investigation as a potential agent for prevention or therapy of oestrogen receptorpositive (ER þ ) breast cancer (Mesfin et al, 2000(Mesfin et al, , 2001Bennett et al, 2002Bennett et al, , 2006DeFreest et al, 2004). After identifying the active site of AFP as an eight-amino acid peptide (Mesfin et al, 2000), Mesfin went on to develop a more stable, cyclised peptide with substantial potential as a pharmaceutical agent (Mesfin et al, 2001).…”

“…Reducing Tam-induced toxicity and providing alternatives to Tam for Tam-resistant tumours would advance the treatment of breast cancer. We have been investigating AFPep for these purposes (Mesfin et al, 2000(Mesfin et al, , 2001Bennett et al, 2002Bennett et al, , 2006DeFreest et al, 2004;Parikh et al, 2005). However, as part of this investigation, it seemed reasonable to evaluate AFPep in combination with Tam in that it might add to the therapeutic activity of Tam, and perhaps might even reduce the toxicity or side effects of Tam.…”