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
✍ Scribed by Brudzynski, Katrina ;Carlone, Robert
- Book ID
- 102337530
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 434 KB
- Volume
- 301A
- Category
- Article
- ISSN
- 0022-104X
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✦ Synopsis
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. J. Exp. Zool. 301A:389–400, 2004. © 2004 Wiley‐Liss, Inc.