Inducing apoptosis in rolling cancer cells: a combined therapy with aspirin and immobilized TRAIL and E-selectin

Mol Pharm. 2012 Aug 6;9(8):2219-27. doi: 10.1021/mp300073j. Epub 2012 Jul 2.

Abstract

Though metastasis is considered an inefficient process, over 90% of cancer related deaths are attributed to the formation of secondary tumors. Thus, eliminating circulating cancer cells could lead to improved patient survival. This study was aimed at exploiting the interactions of cancer cells with selectins under flow to selectively kill captured colon cancer cells. Microtubes functionalized with E-selectin and TRAIL were perfused with colon cancer cell line Colo205 either treated with 1 mM aspirin or untreated for 1 or 2 h. Cells were collected from the microtube and analyzed by flow cytometry. Aspirin treatment alone killed only 3% cells in culture. A 95% difference in the number of cells killed between control and TRAIL + ES surfaces was seen when aspirin treated cells were perfused over the functionalized surface for 2 h. We have demonstrated a novel biomimetic method to capture and neutralize cancer cells in flow, thus reducing the chances for the formation of secondary tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Aspirin / chemistry
  • Aspirin / pharmacology*
  • Cell Line, Tumor
  • E-Selectin / chemistry
  • E-Selectin / pharmacology*
  • Humans
  • Neoplastic Cells, Circulating / drug effects
  • TNF-Related Apoptosis-Inducing Ligand / chemistry
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*

Substances

  • E-Selectin
  • TNF-Related Apoptosis-Inducing Ligand
  • Aspirin