Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors
Sh. Hong et al., Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors, CANCER RES, 59(9), 1999, pp. 2223-2228
Arachidonic acid (AA) metabolizing enzymes are emerging as significant medi
ators of growth stimulation for epithelial cells. The relative contribution
of the various family members of AA metabolizing enzymes to epithelial can
cer cell growth is not known. To study this question, we first analyzed a s
eries of epithelial cancer cells to establish the relative frequency of exp
ression for the various enzymes, We analyzed the expression of five AA meta
bolizing enzymes as well as 5-lipoxygenase activating protein (FLAP) in a p
anel of human epithelial cancer cell lines (n = 20) using reverse transcrip
tion-PCR. From this analysis, we found that cyclooxygenase-l (COX-1), 5-lip
oxygenase (5-LOX), and FLAP were universally expressed in all cancer cell l
ines tested. For the remaining enzymes, the expression of COX-2, 12-LOX, an
d 15-LOX varied among cell lines, 60, 35, and 90%, respectively. Although t
he pattern of expression varied among the different cell types, all of the
enzymes were expressed in all major cancer histologies.
Using a panel of selective biochemical AA metabolizing enzyme inhibitors, w
e then evaluated the effect of these agents on cell lines with known expres
sion status for the AA metabolizing enzymes, For the enzymes that were not
universally expressed, growth inhibition by selective biochemical inhibitor
s did not closely correlate with the expression status of specific enzymes
(P > 0.05), For the universally expressed enzymes, the LOX inhibitors were
more potent growth inhibitors than the COX inhibitors. The frequent express
ion of the AA metabolizing enzymes suggests that AA metabolism pathway may
be modulated in response to xenobiotic exposure during carcinogenesis. Alth
ough establishing a priori AA metabolizing enzyme status was not consistent
ly informative about what AA metabolizing enzyme inhibition would be most g
rowth inhibitory, the frequent inhibition of many epithelial cancers by the
se biochemical inhibitors opens a new avenue for cancer therapy and interve
ntion in carcinogenesis.