title: Selective Targeting of Cancer Stem Cells by 2-Aminodihydroquinoline Analogs.
abstract: Many aminodihydroquinoline compounds have been studied to determine their cytotoxicity to cancer cells. However, anti-cancer stem cells (CSCs) activity of aminodihydroquinoline has not been tested in spite that CSC is believed to do an important roles in chemotherapy resistance and recurrence. The CSC selective targeting activities of 10 recently synthesized 2-aminodihydroquinoline analogs were examined on CSCs and bulk culture of a glioblastoma cell line. A diethylaminopropyl substituted aminodihydroquinoline, 5h, showed a strong anti-CSC effect and general cytotoxicity. However, a benzyl substituted aminodihydroquinoline, 5i, displayed the most effective anti-CSC effect, with no or small significant cytotoxic effect in bulk culture conditions. While 5h temporarily enhanced CSC marker-positive cells and eventually suppressed the CSC population, which is similar to other cytotoxic anticancer reagents reported, 5i selectively eliminated CSC marker-positive cells based on fluorescence activated cell sorter (FACS) analysis. 5h also temporarily activated some genes associated with signaling required for CSC, while 5i selectively suppressed these genes supporting that the differential effects are resulted from different molecular responses. In addition, the selective CSC effect is also found against a colon cancer cell line. Collectively, we suggest that these two novel aminodihydroquinoline compounds possess novel anti-CSC effects in colon and brain tumor derived cell lines probably through independent pathways.
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University.
authors.forename: Heejoo
authors.initials: H
authors.lastname: Park
authors.forename: Yeongji
authors.initials: Y
authors.lastname: Yu
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kim
authors.forename: Eun
authors.initials: E
authors.lastname: Lee
authors.forename: Hani
authors.initials: H
authors.lastname: Lee
authors.forename: Raok
authors.initials: R
authors.lastname: Jeon
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines