title: Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound.
abstract: Tumor progression may be driven by a small subpopulation of cancer stem cells (CSCs characterized by CD44+/CD24-phenotype). We investigated the influence of a newly developed thienopyridine anticancer compound (3-amino-5-oxo-N-naphthyl-5,6,7, 8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide,1) on the growth, survival and glycophenotype (CD15s and GM3 containing neuraminic acid substituted with acetyl residue, NeuAc) of breast and prostate cancer stem/progenitor-like cell population. MDA-MB-231 and Du-145 cells were incubated with compound1alone or in combination with paclitaxel. The cellular metabolic activity was determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The type of cell death induced by 48-h treatment was assessed using a combination of Annexin-V-FITC and propidium iodide staining. Flow cytometric analysis was performed to detect the percentage of CD44+/CD24-cells, and GM3 and CD15s positive CSCs, as well as the expression of GM3 and CD15s per one CSC, in both cell lines. Compound1produces a dose- and time-dependent cytotoxicity, mediated mainly by apoptosis in breast cancer cells, and slightly (2.3%) but statistically significant lowering breast CSC subpopulation. GM3 expression per one breast CSC was increased, and the percentage of prostate GM3+CSC subpopulation was decreased in cells treated with compound1compared with non-treated cells. The percentage of CD15s+CSCs was lower in both cell lines after treatment with compound1. Considering that triple-negative breast cancers are characterized by an increased percentage of breast CSCs and knowing their association with an increased risk of metastasis and mortality, compound1is a potentially effective drug for triple-negative breast cancer treatment.
authors.affiliation: Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia.
authors.forename: Angela
authors.initials: A
authors.lastname: Mastelić
authors.affiliation: Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia.
authors.forename: Vedrana
authors.initials: V
authors.lastname: Čikeš Čulić
authors.affiliation: Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Režić Mužinić
authors.affiliation: Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Vuica-Ross
authors.affiliation: School of Chemical Sciences, The University of Auckland.
authors.forename: David
authors.initials: D
authors.lastname: Barker
authors.affiliation: Auckland Cancer Society Research Centre, The University of Auckland; Molecular Medicine and Pathology Department, The University of Auckland, Auckland, New Zealand.
authors.forename: Euphemia Y
authors.initials: EY
authors.lastname: Leung
authors.affiliation: School of Chemical Sciences, The University of Auckland.
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
authors.affiliation: Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Markotić
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000473:pathology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines; C000618478:thieno(2,3-b)pyridine
keywords: CD15s; CD44+/CD24−; GM3; breast; cancer stem cells; prostate