Zz. Su et al., APOPTOSIS MEDIATES THE SELECTIVE TOXICITY OF CAFFEIC ACID PHENETHYL ESTER (CAPE) TOWARD ONCOGENE-TRANSFORMED RAT EMBRYO FIBROBLAST CELLS, Anticancer research, 15(5), 1995, pp. 1841-1848
The active component of the folk medicine propolis, caffeic acid phene
thyl ester (CAFE), displays selective toxicity toward cloned rat embry
o fibroblast (CREF) cells transformed by a spectrum of diverse acting
oncogenes. identification of the mode of action of CAFE should provide
useful information for possible applications of this compound for can
cer therapy. The present study uses a series of on reverted and CAPE-r
esistant oncogene transformed CREF cells to investigate the mechanism
underlying the increased sensitivity of transformed cells to CAFE. A d
irect relationship exists between the cytotoxic effects of CAPE and th
e induction of DNA fragmentation and apoptosis. DNA degradation into n
ucleosomal fragments and apoptotic shifts in DNA cell cycle profiles o
ccur in CAPE-treated CREF cells transformed by wildtype 5 adenovirus (
Ad5), a mutant Ad5 (H5hr1), the wild-type Ad5 EIA transforming gene, v
-si c, Ha-ras and the human papilloma virus type 18 transforming genes
(HPV-18). In contrast, untransformed CREF cells, human fibroblast exp
ression library-induced morphological revertants of Ad5- and v-src-tra
nsformed CREF cells, and Krev-1 expressing revertant Ha-ras-transforme
d CREF cells nl resistant to CAFE-induced toxicity and apoptosis. Simi
larly, mutant Ad5-transformed CREF cells selected by step-wise growth
in increasing concentrations of CAFE are resistant to growth inhibitio
n and apoptosis induced by CAFE. These findings indicate that expressi
on of the transformed phenotype by rodent cells evokes sensitivity to
CAFE induced toxicity through apoptosis. The acquisition of CAFE sensi
tivity in rodent cells is independent of the mode of action of the onc
ogenic agent. CAFE may prove useful as an antiproliferative agent in c
ancel cells transformed by mechanistically diverse acting oncogenes.