Hanaki Yusuke, Shikata Yuki, Kikumori Masayuki, Hotta Natsuki, Imoto Masaya, Irie Kazuhiro
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):438-445. doi: 10.1016/j.bbrc.2017.11.052. Epub 2017 Nov 9.
10-Me-aplog-1 is a simplified analog of the tumor-promoting compound debromoaplysiatoxin (DAT) and a unique protein kinase C (PKC) activator with limited tumor-promoting and pro-inflammatory activities. 10-Me-aplog-1 inhibits the growth of several cancer cell lines, but the inhibitory mechanism involving PKC isozymes remains unclear. We quantified the amount of PKC isozymes in nine human cancer cell lines that differ in 10-Me-aplog-1 sensitivity. PKCα and δ were the predominant isozymes expressed in all cell lines, but there was no significant correlation between expression levels and anti-proliferative activity. Knocking down PKCα, and/or PKCδ in the three aplog-sensitive cell lines indicated their involvement in the anti-proliferative and pro-apoptotic activities of 10-Me-aplog-1. This finding suggests that PKCα and/or PKCδ activation could be effective for treating certain cancers. Since the mechanism underlying 10-Me-aplog-1's anti-proliferative activities resembles that of DAT, 10-Me-aplog-1 may be regarded as a special key derived from pleiotropic DAT as a bunch of keys.
10-甲基脱溴海兔毒素-1是促肿瘤化合物脱溴海兔毒素（DAT）的一种简化类似物，是一种独特的蛋白激酶C（PKC）激活剂，具有有限的促肿瘤和促炎活性。10-甲基脱溴海兔毒素-1可抑制多种癌细胞系的生长，但涉及PKC同工酶的抑制机制仍不清楚。我们对九种对10-甲基脱溴海兔毒素-1敏感性不同的人癌细胞系中的PKC同工酶量进行了定量。PKCα和δ是所有细胞系中表达的主要同工酶，但表达水平与抗增殖活性之间没有显著相关性。在三种对脱溴海兔毒素敏感的细胞系中敲低PKCα和/或PKCδ表明它们参与了10-甲基脱溴海兔毒素-1的抗增殖和促凋亡活性。这一发现表明PKCα和/或PKCδ的激活可能对治疗某些癌症有效。由于10-甲基脱溴海兔毒素-1抗增殖活性的潜在机制与DAT相似，10-甲基脱溴海兔毒素-1可被视为从多效性的DAT衍生出的一把特殊的钥匙，而DAT则是一串钥匙。
