Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3- b]pyridine anticancer compound

Drug Des Devel Ther. 2017 Mar 14:11:759-769. doi: 10.2147/DDDT.S121122. eCollection 2017.

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: CD15s; CD44+/CD24−; GM3; breast; cancer stem cells; prostate.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Male
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • Prostatic Neoplasms / pathology*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Time Factors

Substances

  • Antineoplastic Agents
  • Pyridines
  • thieno(2,3-b)pyridine