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  • Title: Stage-dependent modulation of limb regeneration by caffeic acid phenethyl ester (CAPE)--immunocytochemical evidence of a CAPE-evoked delay in mesenchyme formation and limb regeneration.
    Author: Brudzynski K, Carlone R.
    Journal: J Exp Zool A Comp Exp Biol; 2004 May 01; 301(5):389-400. PubMed ID: 15114646.
    Abstract:
    Caffeic acid phenethyl ester (CAPE), a natural compound of bee propolis, selectively inhibits proliferation of transformed cells in several cancer models in vitro. To examine in vivo CAPE function, we used the newt regeneration blastema as a model system wherein the processes of de-differentiation and subsequent proliferation of undifferentiated cells mimic changes associated with oncogenic transformation and tumorigenesis. We have shown that a single dose of CAPE significantly increased cell proliferation at the stages of blastema growth and re-differentiation. At the de-differentiation stage, CAPE significantly stimulated proliferation of wound epidermis keratinocytes, but decreased proliferation in the blastema mesenchyme. Immunohistochemistry with a mesenchymal cell marker, vimentin, revealed a highly significant reduction of vimentin staining in the mesenchyme of CAPE-treated regenerates (p<0.001). These results, together with morphological observations indicate that, at the de-differentiation stage, CAPE stimulated wound re-epithelization, increased keratinocyte proliferation and increased thickness of the wound epidermis. However, CAPE inhibited mesenchyme formation and proliferation. The functional consequence of the CAPE inhibitory action was a delay in limb regeneration.
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