Ohtsuki K, Tanoue S, Karino A
Laboratory of Genetical Biochemistry, Kitasato University, School of Allied Health Sciences.
Gan To Kagaku Ryoho. 1997 Feb;24(4):443-53.
A NCS-chromophore (molecular weight: approximately 695) can be extracted from an antitumor antibiotic neocarzinostatin (NCS) (approximately 11,000, pI 3.3) with methanol as a DNA cleavaging molecule. Recently, the Goldberg research group (Harvard University, USA) proposed two distinct mechanisms of DNA cleavages (thiol-dependent DNA cleavage and thiol-independent base-catalyzed (bc) cleavage of ssDNA) by NCS-chromophore in vitro. Therefore, it is concluded that the ability of NCS-chromophore to cleave DNA is its primary action, which selectively inhibits DNA synthesis in cultured cells. Furthermore, we found that NCS-chromophore inhibits protein phosphorylation by CK-II (casein kinase II) involved in transcriptional regulation in a dose-dependent manner. Disruption of the repair systems of the NCS-chromophore-induced biological damages results in the positive induction of apoptosis, because the drug is greatly activated by thiols at the intracellular level, and it inhibits the activities of several transcriptional factors through their specific phosphorylation by nuclear kinases, such as CK-II. Taken together, all these biological and biochemical data suggest that the NCS-chromophore could be an effective chemotherapeutic drug for human cancer if its toxicity can be appropriately controlled.
一种NCS发色团（分子量：约695）可以作为一种DNA切割分子，用甲醇从抗肿瘤抗生素新制癌菌素（NCS）（约11,000，pI 3.3）中提取出来。最近，戈德堡研究小组（美国哈佛大学）提出了NCS发色团在体外切割DNA的两种不同机制（硫醇依赖性DNA切割和单链DNA的硫醇非依赖性碱催化（bc）切割）。因此，可以得出结论，NCS发色团切割DNA的能力是其主要作用，它能选择性地抑制培养细胞中的DNA合成。此外，我们发现NCS发色团以剂量依赖性方式抑制参与转录调控的酪蛋白激酶II（CK-II）介导的蛋白质磷酸化。NCS发色团诱导的生物损伤修复系统的破坏导致凋亡的正向诱导，因为该药物在细胞内水平上被硫醇极大地激活，并且它通过核激酶（如CK-II）对几种转录因子的特异性磷酸化来抑制其活性。综上所述，所有这些生物学和生物化学数据表明，如果能适当控制其毒性，NCS发色团可能是一种有效的人类癌症化疗药物。
