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- W2014179915 abstract "Daphnetoxin, a mezerein derivative, was isolated from the stem bark of Daphne gnidium. Mezerein is a PKC activator that exhibits antileukemic properties. However, daphnetoxin and its analogue 12-hydroxydaphnetoxin were described as being devoid of this effect. In the present study daphnetoxin and mezerein were compared as PKC activators on classical (alpha and beta I), novel (delta) and atypical (zeta) isoforms, using an alternative in vivo yeast phenotypic assay. The aim was to clarify if daphnetoxin is a PKC activator and if the differences between the antiproliferative effect of mezerein and of its analogue daphnetoxin may be ascribed to differences on their potency or selectivity as PKC activators. Yeast samples expressing each of the mammalian PKC isoforms tested were incubated with daphnetoxin or mezerein. Growth inhibition caused by these drugs was assumed to be due to PKC activation since it did not occur when expression was not induced. Mezerein inhibited the growth of yeast expressing PKC alpha (IC(50) = 1190 +/- 237 nM; n = 20), PKC beta I (IC(50) = 908 +/- 46 nM; n = 20), and PKC delta (IC(50) = 141 +/- 25 nM; n = 20) but not of yeast expressing PKC zeta. Daphnetoxin also inhibited the growth of yeast expressing isoforms alpha, beta I and delta, being more potent than mezerein on PKC alpha (IC(50) = 536 +/- 183 nM; n = 20; P < 0.05), as potent as mezerein on PKC beta I (IC(50) = 902 +/- 129 nM; n = 20) and less potent than mezerein upon PKC delta (IC(50) = 3370 +/- 492 nM; n = 20; P < 0.05). These results show that daphnetoxin is a potent PKC activator but with a selectivity different from that of mezerein. It is suggested that the lack of antileukemic and antiproliferative effects of daphnetoxin may be due to its lower potency to activate PKC delta." @default.
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- W2014179915 date "2001-12-01" @default.
- W2014179915 modified "2023-10-18" @default.
- W2014179915 title "Differential Activation by Daphnetoxin and Mezerein of PKC-Isotypes α, βI, δ and ζ" @default.
- W2014179915 doi "https://doi.org/10.1055/s-2001-18843" @default.
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