Nk. Mak et al., Expression of protein kinase C isoforms in euxanthone-induced differentiation of neuroblastoma cells, PLANTA MED, 67(5), 2001, pp. 400-405
Euxanthone, a potent neuritogenic compound isolated from the roots of the m
edicinal herb Polygala caudata, has recently been shown to induce the diffe
rentiation of murine neuroblastoma Neuro ZA (BU-l) cells. In this study, th
e role of protein kinase C (PKC) and the expression of various PKC isoforms
in euxanthone-treated BU-l cells were examined. mRNA phenotyping using the
reverse-transcription polymerase chain reaction (RT-PCR) showed that BU-1
cells express six different PKC isoforms, namely PKC-alpha, -beta, -delta,
-epsilon, -lambda, and -zeta. Differential regulation and expression of PKC
isoforms was observed in BU-1 cells treated with 100 muM euxanthone. PKC-a
lpha, -beta, -delta, -lambda and -zeta were all up-regulated, with 1.7- to
9.5-fold increase, at around 30 to 60 minutes after euxanthone treatment. T
he expression level of PKC-epsilon remained relatively constant during the
treatment. PKC-gamma, -eta, and -Theta were not detected in both untreated
and euxanthone-treated BU-1 cells. Staurosporine. a broad spectrum PKC inhi
bitor, was found to inhibit both spontaneous and euxanthone-induced neurito
genesis in BU-l cells. A significant reduction of the euxanthone-induced ne
uritogenic effect was also observed when the PKC isoform-specific inhibitor
Go6976 was included in the culture. These results suggest that the euxanth
one-induced differentiation of the neuroblastoma BU-l cells may be mediated
through the differential expression of PKC-alpha, -beta, -delta, -lambda a
nd -zeta isoforms.