Shiono Yoshihito, Shiono Nobuyo, Seo Shujiro, Oka Syuichi, Yamazaki Yoshimitsu
Research Institute of Biological Resources, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
Z Naturforsch C J Biosci. 2002 Sep-Oct;57(9-10):923-9. doi: 10.1515/znc-2002-9-1028.
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.
从硫黄链霉菌的培养液中分离出一种四羟基蒽酮衍生物——抗霉素，从贯叶连翘提取物中分离出一种类似的多酚二蒽醌——金丝桃素，它们作为细胞凋亡的调节剂。抗霉素在人巨核母细胞白血病CMK - 7细胞中，能抑制放线菌素D（AD）诱导的细胞凋亡，无论有无秋水仙酰胺（CL）加速作用，其对AD诱导凋亡的抑制IC50约为0.5微摩尔，对AD加CL诱导凋亡的抑制IC50约为1微摩尔。单独的CL诱导细胞轻微凋亡，抗霉素可增强此作用。金丝桃素不抑制AD诱导的凋亡，且轻微增强CL诱导的凋亡。大黄素相当于金丝桃素中2个蒽醌单元之一，对该凋亡系统无任何作用。AD诱导的凋亡受到抗氧化黄酮类化合物木犀草素（IC50 45微摩尔）和蛋白激酶C（PKC）抑制剂星形孢菌素（IC50 1.5微摩尔）的抑制，但这些化合物不影响CL诱导的凋亡。金丝桃素和抗霉素清除超氧阴离子自由基的速率与木犀草素相同。金丝桃素和木犀草素可抑制CMK - 7细胞中的PKC，但抗霉素对其抑制作用不明显。该结果表明，抗霉素对AD诱导凋亡的抑制至少部分与其抗氧化活性相关，且该化合物对CL诱导凋亡的增强作用取决于其缺乏PKC抑制活性。虽然机制尚不清楚，但在金丝桃素和木犀草素的情况下，PKC抑制可能会阻碍CL诱导凋亡的增强。
