Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Biological Science, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-hiroshima, Hiroshima, 739-8526, Japan.
Sci Rep. 2019 Jan 31;9(1):1096. doi: 10.1038/s41598-018-36608-5.
The discovery of anticancer therapeutics effective in eliminating dormant cells is a significant challenge in cancer biology. Here, we describe new synthetic polymer-based anticancer agents that mimic the mode of action of anticancer peptides. These anticancer polymers developed here are designed to capture the cationic, amphiphilic traits of anticancer peptides. The anticancer polymers are designed to target anionic lipids exposed on the cancer cell surfaces and act by disrupting the cancer cell membranes. Because the polymer mechanism is not dependent on cell proliferation, we hypothesized that the polymers were active against dormant cancer cells. The polymers exhibited cytotoxicity to proliferating prostate cancer. Importantly, the polymer killed dormant prostate cancer cells that were resistant to docetaxel. This study demonstrates a new approach to discover novel anticancer therapeutics.
发现能够有效消除休眠细胞的抗癌疗法是癌症生物学的一个重大挑战。在这里,我们描述了新的基于合成聚合物的抗癌剂,这些抗癌剂模拟了抗癌肽的作用模式。这些新开发的抗癌聚合物旨在捕获抗癌肽的阳离子、两亲特性。抗癌聚合物旨在靶向暴露在癌细胞表面的阴离子脂质,并通过破坏癌细胞膜起作用。由于聚合物的作用机制不依赖于细胞增殖,我们假设聚合物对休眠癌细胞具有活性。聚合物对增殖的前列腺癌细胞表现出细胞毒性。重要的是,该聚合物杀死了对多西他赛有抗药性的休眠前列腺癌细胞。这项研究展示了一种发现新型抗癌疗法的新方法。