title: Enzyme-Regulated Supramolecular Assemblies of Cholesterol Conjugates against Drug-Resistant Ovarian Cancer Cells.
abstract: 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.
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Huaimin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Zhaoqianqi
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Fritzsching
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Mike
authors.initials: M
authors.lastname: Rigney
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmidt-Rohr
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02453, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004798:Enzymes / Q000378:metabolism*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D019000:Phosphotyrosine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004798:Enzymes; D019000:Phosphotyrosine; D002784:Cholesterol