Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer

乙酰化 微管 三阴性乳腺癌 乙酰转移酶 癌细胞 微管蛋白 化学 癌症研究 细胞 细胞生物学 生物 癌症 生物化学 乳腺癌 遗传学 基因
作者
Ahreum Kwon,Gwi Bin Lee,Taein Park,Jeong Hoon Lee,Panseon Ko,Eunae You,Jin Hee Ahn,Soo Hyun Eom,Sangmyung Rhee,Woo Keun Song
出处
期刊:Biomedicines [Multidisciplinary Digital Publishing Institute]
卷期号:8 (9): 338-338 被引量:18
标识
DOI:10.3390/biomedicines8090338
摘要

Microtubules are one of the major targets for anticancer drugs because of their role in cell proliferation and migration. However, as anticancer drugs targeting microtubules have side effects, including the death of normal cells, it is necessary to develop anticancer agents that can target microtubules by specifically acting on cancer cells only. In this study, we identified chemicals that can act as anticancer agents by specifically binding to acetylated microtubules, which are predominant in triple-negative breast cancer (TNBC). The chemical compounds disrupted acetylated microtubule lattices by interfering with microtubule access to alpha-tubulin acetyltransferase 1 (αTAT1), a major acetyltransferase of microtubules, resulting in the increased apoptotic cell death of MDA-MB-231 cells (a TNBC cell line) compared with other cells, such as MCF-10A and MCF-7, which lack microtubule acetylation. Moreover, mouse xenograft experiments showed that treatment with the chemical compounds markedly reduced tumor growth progression. Taken together, the newly identified chemical compounds can be selective for acetylated microtubules and act as potential therapeutic agents against microtubule acetylation enrichment in TNBC.
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