AS602801, an Anti-Cancer Stem Cell Drug Candidate, Suppresses Gap-junction Communication Between Lung Cancer Stem Cells and Astrocytes

Anticancer Res. 2018 Sep;38(9):5093-5099. doi: 10.21873/anticanres.12829.

Abstract

Background/aim: Cancer stem cells (CSCs) are associated with tumorigenesis, recurrence, and metastasis. Cell-cell communication via gap junctions (GJs) between metastatic cancer cells and astrocytes is necessary for brain metastasis. Agents targeting communication between CSCs and astrocytes are expected to suppress brain metastasis.

Materials and methods: Using the A549 CSC, a cancer stem-like cell derived from A549, we examined the effect of AS602801, an anti-cancer stem cell agent whose safety has been confirmed in a phase 2 clinical trial, on GJ communication and connexin expression using a dye-transfer assay and immunoblot analysis, respectively.

Results: AS602801 specifically suppressed cell-cell communication in A549 CSCs without any suppression of GJ communication in astrocytes; it also decreased the expression of connexin 43, a constituent of GJs, in A549 CSCs.

Conclusion: The anti-cancer stem cell agent, AS602801, is a potential drug candidate against brain metastasis.

Keywords: AS602801; CSC; Cell–cell interaction; astrocytes; metastasis.

MeSH terms

  • A549 Cells
  • Animals
  • Astrocytes / cytology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Benzothiazoles / pharmacology*
  • Brain Neoplasms / prevention & control
  • Cell Communication / drug effects
  • Connexin 43 / metabolism*
  • Down-Regulation
  • Gap Junctions / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Neoplastic Stem Cells / cytology*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Pyrimidines / pharmacology*
  • Rats

Substances

  • Benzothiazoles
  • Connexin 43
  • GJA1 protein, human
  • Pyrimidines
  • bentamapimod