Antiestrogenic and anticancer activities of peptides derived from the active site of alpha-fetoprotein

Cyclo[EKTOVNOGN] (AFPep), a cyclic 9-amino acid peptide derived from the active site of alpha-fetoprotein, has been shown to prevent carcinogen-induced mammary cancer in rats and inhibit the growth of ER+ human breast cancer xenografts in mice. Recently, studies using replica exchange molecular dynamics predicted that the TOVN region of AFPep might form a dynamically stable putative Type I beta-turn, and thus be biologically active without additional amino acids. The studies presented in this paper were performed to determine whether TOVN and other small analogs of AFPep would inhibit estrogen-stimulated cancer growth and exhibit a broad effective-dose range. These peptides contained nine or fewer amino acids, and were designed to bracket or include the putative pharmacophoric region (TOVN) of AFPep. Biological activities of these peptides were evaluated using an immature mouse uterine growth inhibition assay, a T47D breast cancer cell proliferation assay, and an MCF-7 breast cancer xenograft assay. TOVN had very weak antiestrogenic activity in comparison to AFPep's activity, whereas TOVNO had antiestrogenic and anticancer activities similar to AFPep. OVNO, which does not form a putative Type I beta-turn, had virtually no antiestrogenic and anticancer activities. A putative proteolytic cleavage product of AFPep, TOVNOGNEK, significantly inhibited E2-stimulated growth in vivo and in vitro over a wider dose range than AFPep or TOVNO. We conclude that TOVNO has anticancer potential, that TOVNOGNEK is as effective as AFPep in suppressing growth of human breast cancer cells, and that it does so over a broader effective-dose range.

Review of Nineteenth-Century Geographies: The Transformation of Space from the Victorian Age to the American Century, eds. H. Michie and R. Thomas

It is by now a banal observation that published collections of conference papers tend to add up to a whole that is considerably less than the sum of the parts. Nineteenth-Century Geographies, a book that grew out of an interdisciplinary conference held at Rice University in 1998 falls into this category. While assuring my readers that each individual contribution is independently worth a read is likewise a predictable cliché, it is in fact the case that every one of the 17 articles collected here—notwithstanding the rather convoluted Introduction—has much to offer the study, broadly speaking, of ‘cultural spaces’ of British and American imperialisms in the nineteenth century. . . . All of my complaints aside, this turns out to be a much more enjoyable book to read than to review, and I would recommend skimming and dipping at length. I cannot quite imagine when a read-through of this book might be called for, except perhaps in graduate seminars on related topics.