A highly polar xanthophyll of 9′-cis -neoxanthin induces apoptosis in HCT116 human colon cancer cells through mitochondrial dysfunction

Masaru Terasaki, Akira Asai, Hong Zhang, Akihiko Nagao

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Highly polar xanthophylls of 9′-cis-neoxanthin (neoxanthin) and fucoxanthin, which have the characteristic structure of an epoxy group and an allenic bond, were previously found to induce apoptosis in human prostate cancer cells. In the present study, we found apoptosis induction by neoxanthin in HCT116 human colon cancer cells and examined the induction mechanism. The cells exposed to 20 μM neoxanthin clearly showed chromatin condensation, DNA fragmentation, and an increase in hypodiploid cells. Neoxanthin treatment increased the activities of caspase-3, -8 and -9, and the protein levels of their active subunits, except in the case of caspase-8. The treatment also caused the loss of mitochondrial transmembrane potential at an early stage and subsequently the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to cytosol. The exposure of neoxanthin directly to mitochondria isolated from the cells enhanced the release of cytochrome c and AIF in a dose-dependent manner. Approximately 50% of the neoxanthin taken up into the HCT116 cells accumulated in the mitochondrial fraction. These results suggest that the accumulation of neoxanthin in mitochondria causes the loss of mitochondrial transmembrane potential and thereafter releases cytochrome c and AIF, leading to the execution of apoptosis.

Original languageEnglish
Pages (from-to)227-237
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume300
Issue number1-2
DOIs
Publication statusPublished - 2007 Jun 1
Externally publishedYes

Keywords

  • AIF
  • Apoptosis
  • Cytochromec
  • Mitochondrial transmembrane potential
  • Neoxanthin

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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