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.
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.
Brudzynski
Katrina
K
Bee-Biomedicals Inc. St. Catharines, Ontario, Canada L2T 3T4.
Carlone
Robert
R
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D002109:Caffeic Acids / Q000494:pharmacology*; D005121:Extremities / Q000033:anatomy & histology / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology; D008648:Mesoderm / Q000187:drug effects* / Q000502:physiology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D012455:Salamandridae; D013936:Thymidine; D014316:Tritium; D014746:Vimentin; D014945:Wound Healing / Q000187:drug effects
D002109:Caffeic Acids; D014746:Vimentin; D014316:Tritium; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D013936:Thymidine