Enzyme-Regulated Supramolecular Assemblies of Cholesterol Conjugates against Drug-Resistant Ovarian Cancer Cells

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• 作者：Huaimin Wang ; Zhaoqianqi Feng ; Dongdong Wu ; Keith J. Fritzsching ; Mike Rigney ; Jie Zhou ; Yujie Jiang ; Klaus Schmidt-Rohr ; Bing Xu
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：August 31, 2016
• 年：2016
• 卷：138
• 期：34
• 页码：10758-10761
• 全文大小：354K
• 年卷期：0
• ISSN：1520-5126

文摘

We report that phosphotyrosine–cholesterol conjugates effectively and selectively kill cancer cells, including platinum-resistant ovarian cancer cells. The conjugate increases the degree of noncovalent oligomerization upon enzymatic dephosphorylation in aqueous buffer. This enzymatic conversion also results in the assembly of the cholesterol conjugates inside and outside cells and leads to cell death. Preliminary mechanistic studies suggest that the formed assemblies of the conjugates not only interact with actin filaments and microtubules but also affect lipid rafts. As the first report of multifaceted supramolecular assemblies of cholesterol conjugates against cancer cells, this work illustrates the integration of enzyme catalysis and self-assembly of essential biological small molecules on and inside cancer cells as a promising strategy for developing multifunctional therapeutics to treat drug-resistant cancers.