Effects of Polyphenolic Anthrone Derivatives, Resistomycin and Hypericin, on Apoptosis in Human Megakaryoblastic Leukemia CMK-7 Cell Line

Yoshihito Shiono, Nobuyo Shiono, Shujiro Seo, Syuichi Oka, Yoshimitsu Yamazaki
2002 Zeitschrift für Naturforschung C - A Journal of Biosciences  
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 μm and IC50 for inhibition
more » ... C50 for inhibition against AD plus CL-induced apoptosis was about 1 μm. CL alone induced weak apoptosis in cells, which was enhanced by resistomycin. Hypericin did not inhibit AD-induced apoptosis and slightly enhanced CLinduced 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 μm), and a protein kinase C (PKC) inhibitor, staurosporine (IC50 1.5 μm), 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 CLinduced 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.
doi:10.1515/znc-2002-9-1028 fatcat:hp7pdzlhjffv5lx5lkx7fsq5uq