Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound
Angela Mastelić,1 Vedrana Čikeš Čulić,1 Nikolina Režić Mužinić,1 Milena Vuica-Ross,2 David Barker,3 Euphemia Y Leung,4,5 Jóhannes Reynisson,3 Anita Markotić1 1Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia; 2Department...
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doaj-bcce1cc04f5a49869d1e6164719c1ff92020-11-24T23:10:36ZengDove Medical PressDrug Design, Development and Therapy1177-88812017-03-01Volume1175976931817Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compoundMastelić AČikeš Čulić VRežić Mužinić NVuica-Ross MBarker DLeung EYReynisson JMarkotić AAngela Mastelić,1 Vedrana Čikeš Čulić,1 Nikolina Režić Mužinić,1 Milena Vuica-Ross,2 David Barker,3 Euphemia Y Leung,4,5 Jóhannes Reynisson,3 Anita Markotić1 1Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia; 2Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; 3School of Chemical Sciences, The University of Auckland, 4Auckland Cancer Society Research Centre, The University of Auckland, 5Molecular Medicine and Pathology Department, The University of Auckland, Auckland, New Zealand 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 compound 1 alone 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. Compound 1 produces 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 compound 1 compared with non-treated cells. The percentage of CD15s+ CSCs was lower in both cell lines after treatment with compound 1. 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, compound 1 is a potentially effective drug for triple-negative breast cancer treatment. Keywords: breast, prostate, cancer stem cells, CD44+/CD24-, GM3, CD15shttps://www.dovepress.com/glycophenotype-of-breast-and-prostate-cancer-stem-cells-treated-with-t-peer-reviewed-article-DDDTbreastprostatecancer stem cellsCD44+/CD24-GM3CD15s |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mastelić A Čikeš Čulić V Režić Mužinić N Vuica-Ross M Barker D Leung EY Reynisson J Markotić A |
spellingShingle |
Mastelić A Čikeš Čulić V Režić Mužinić N Vuica-Ross M Barker D Leung EY Reynisson J Markotić A Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound Drug Design, Development and Therapy breast prostate cancer stem cells CD44+/CD24- GM3 CD15s |
author_facet |
Mastelić A Čikeš Čulić V Režić Mužinić N Vuica-Ross M Barker D Leung EY Reynisson J Markotić A |
author_sort |
Mastelić A |
title |
Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound |
title_short |
Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound |
title_full |
Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound |
title_fullStr |
Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound |
title_full_unstemmed |
Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound |
title_sort |
glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-b]pyridine anticancer compound |
publisher |
Dove Medical Press |
series |
Drug Design, Development and Therapy |
issn |
1177-8881 |
publishDate |
2017-03-01 |
description |
Angela Mastelić,1 Vedrana Čikeš Čulić,1 Nikolina Režić Mužinić,1 Milena Vuica-Ross,2 David Barker,3 Euphemia Y Leung,4,5 Jóhannes Reynisson,3 Anita Markotić1 1Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia; 2Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; 3School of Chemical Sciences, The University of Auckland, 4Auckland Cancer Society Research Centre, The University of Auckland, 5Molecular Medicine and Pathology Department, The University of Auckland, Auckland, New Zealand 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 compound 1 alone 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. Compound 1 produces 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 compound 1 compared with non-treated cells. The percentage of CD15s+ CSCs was lower in both cell lines after treatment with compound 1. 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, compound 1 is a potentially effective drug for triple-negative breast cancer treatment. Keywords: breast, prostate, cancer stem cells, CD44+/CD24-, GM3, CD15s |
topic |
breast prostate cancer stem cells CD44+/CD24- GM3 CD15s |
url |
https://www.dovepress.com/glycophenotype-of-breast-and-prostate-cancer-stem-cells-treated-with-t-peer-reviewed-article-DDDT |
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