A paraptosis-like cell death induced by δ-tocotrienol in human colon carcinoma SW620 cells is associated with the suppression of the Wnt signaling pathway

Toxicology. 2011 Jul 11;285(1-2):8-17. doi: 10.1016/j.tox.2011.03.011. Epub 2011 Mar 29.

Abstract

Tocotrienol is considered a beneficial effect agent on inhibition of tumor development. In this study, we focused on the effects of δ-tocotrienol and its possible mechanism on induction of death in human colon cancer SW620 cells. δ-Tocotrienol inhibited proliferation of SW620 cell in a dose-dependent manner. Our findings showed that δ-tocotrienol effectively induced paraptosis-like death in SW620 cells, correlated with the vacuolation that may be from welling and fusion of mitochondria and/or the endoplasmic reticulum (ER) as well as caspase-3 nonactivated. However, there were no changes in apoptosis based on flow cytometry analysis. Of being noted, δ-tocotrienol reduced the expression of β-catenin and wnt-1 proteins by about 50% at the highest dose (20μmol/L). δ-Tocotrienol also decreased cyclin D1, c-jun and MMP-7 protein levels in SW620 cells. Altogether, these data indicate that δ-tocotrienol induces paraptosis-like cell death, which is associated with the suppression of the Wnt signaling pathway. Thus, our findings may provide a novel application in treatment of human colon carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Mitochondria / metabolism
  • Signal Transduction / drug effects
  • Vitamin E / administration & dosage
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology
  • Wnt Proteins / antagonists & inhibitors*
  • Wnt Proteins / drug effects
  • Wnt1 Protein / antagonists & inhibitors

Substances

  • Wnt Proteins
  • Wnt1 Protein
  • Vitamin E
  • tocotrienol, delta
  • Caspase 3