A tetrahydroxyanthrone derivative,
resistomycin, was isolated from the culture broth of Streptomyces sulphureus and a similar polyphenolic dianthraquinone,
hypericin, was isolated from an extract of Hypericum perforatum L. as modulators for apoptosis.
Resistomycin inhibited apoptosis induced by
actinomycin D (AD) with or without acceleration by
colcemid (CL) in human megakaryoblastic
leukemia CMK-7 cells, IC50 for inhibition against AD-induced apoptosis was about 0.5 microM and IC50 for inhibition against AD plus CL-induced apoptosis was about 1 microM. CL alone induced weak apoptosis in cells, which was enhanced by
resistomycin.
Hypericin did not inhibit AD-induced apoptosis and slightly enhanced CL-induced apoptosis.
Emodin, corresponding to 1 of 2
anthraquinone units in
hypericin, did not show any effect on this apoptotic system. AD-induced apoptosis was inhibited by the antioxidative
flavonoid,
luteolin (IC50 45 microM), and a
protein kinase C (PKC) inhibitor,
staurosporine (IC50 1.5 microM), but these compounds did not affect the CL-induced apoptosis.
Hypericin and
resistomycin scavenged
superoxide anion radicals at the same rate as
luteolin. PKC in CMK-7 cells was inhibited by
hypericin and
luteolin, but not significantly inhibited by
resistomycin. This result suggests that the inhibition of AD-induced apoptosis by
resistomycin is at least partly correlated with its antioxidative activity, and that the enhancement of CL-induced apoptosis by this compound depends upon the lack of PKC inhibitory activity. Though the mechanism is not clear, the enhancement of the CL-induced apoptosis might be hindered by PKC inhibition in the case of
hypericin and
luteolin.