Komori A, Suganuma M, Okabe S, Zou X, Tius M A, Fujiki H
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Res. 1993 Aug 1;53(15):3462-4.
A synthetic compound named canventol, 2-isopropyl-4-isopropylidencyclohex-2-ene-1-ol, inhibited tumor promotion of okadaic acid on mouse skin initiated with 7,12-dimethylbenz(a)anthracene in two-stage carcinogenesis experiments more strongly than sarcophytol A, isolated from a soft coral, although canventol has a simpler structure than sarcophytol A. Their mechanisms of action were studied based on our recent evidence that tumor necrosis factor alpha release induced by okadaic acid is an essential mechanism of tumor promotion. Canventol inhibited mouse tumor necrosis factor alpha release from BALB/3T3 cells less strongly than sarcophytol A, indicating that canventol has additional activity. Canventol inhibited isoprenylation of proteins with various molecular weights, such as M(r) 22,000, 17,000, and 13,000, whereas sarcophytol A did not show significant inhibition. Thus, a potent anticarcinogenic activity of canventol is mediated through the inhibitory bifunctions of tumor necrosis factor alpha release and of protein isoprenylation. Since canventol is less toxic to cells than sarcophytol A, these bifunctions are useful markers for screening for new cancer chemopreventive agents.
一种名为坎文托（canventol）的合成化合物，即2-异丙基-4-异亚丙基环己-2-烯-1-醇，在两阶段致癌实验中，对由7,12-二甲基苯并(a)蒽引发的小鼠皮肤，抑制冈田酸（okadaic acid）的肿瘤促进作用比从软珊瑚中分离出的肉珊瑚醇A（sarcophytol A）更强，尽管坎文托的结构比肉珊瑚醇A更简单。基于我们最近的证据，即冈田酸诱导的肿瘤坏死因子α释放是肿瘤促进的一个重要机制，对它们的作用机制进行了研究。坎文托抑制BALB/3T3细胞释放小鼠肿瘤坏死因子α的能力比肉珊瑚醇A弱，这表明坎文托具有额外的活性。坎文托抑制了各种分子量蛋白质的异戊二烯化，如分子量为22,000、17,000和13,000的蛋白质，而肉珊瑚醇A没有显示出明显的抑制作用。因此，坎文托强大的抗癌活性是通过抑制肿瘤坏死因子α释放和蛋白质异戊二烯化这两种功能介导的。由于坎文托对细胞的毒性比肉珊瑚醇A小，这些双重功能是筛选新型癌症化学预防剂的有用标志物。
