新型吲哚基查耳酮靶向微管相关蛋白，诱导癌细胞死亡。
Novel indolyl-chalcones target stathmin to induce cancer cell death.
作者信息
Wegiel Barbara, Wang Yiqiang, Li Mailin, Jernigan Finith, Sun Lijun
机构信息
a Department of Surgery , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
b Transplant Institute & Cancer Research Institute, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.
出版信息
Cell Cycle. 2016 May 2;15(9):1288-94. doi: 10.1080/15384101.2016.1160980. Epub 2016 Mar 17.
Efficacy of current therapies for advanced and metastatic cancers remains a challenge in clinical practice. We investigated the anti-cancer potency of 3 novel indoly-chalcones (CITs). Our results indicated the lead molecule CIT-026 (Formula = C20H16FNO) induced cell death in prostate and lung cancer cell lines at sub-micromolar concentration. CITs (CIT-026, CIT-214, CIT-223) lead to microtubule destabilization, cell death and low cell proliferation, which in part was dependent on stathmin (STMN1) expression. Knockdown of STMN1 with siRNA against STMN1 in part restored viability of cancer cells in response to CITs. Further, CIT-026 and CIT-223 blocked cancer cell invasion through matrigel-coated chambers. Mechanistically, CITs inhibited phosphorylation of STMN1 leading to STMN1 accumulation and mitotic catastrophe. In summary, we have synthetized novel anti-cancer CIT molecules and defined their mechanism of action in vitro.
目前针对晚期和转移性癌症的治疗方法在临床实践中仍然是一个挑战。我们研究了3种新型吲哚基查耳酮（CITs）的抗癌效力。我们的结果表明，先导分子CIT-026（分子式 = C20H16FNO）在亚微摩尔浓度下可诱导前列腺和肺癌细胞系发生细胞死亡。CITs（CIT-026、CIT-214、CIT-223）导致微管去稳定化、细胞死亡和低细胞增殖，这部分依赖于Stathmin（STMN1）的表达。用针对STMN1的siRNA敲低STMN1部分恢复了癌细胞对CITs的反应能力。此外，CIT-026和CIT-223通过基质胶包被的小室阻断癌细胞侵袭。从机制上讲，CITs抑制STMN1的磷酸化，导致STMN1积累和有丝分裂灾难。总之，我们合成了新型抗癌CIT分子并在体外确定了它们的作用机制。
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