Trans 10, cis 12-conjugated linoleic acid induces mitochondria-related apoptosis and lysosomal destabilization in rat hepatoma cells

Masao Yamasaki, Yumi Miyamoto, Hitomi Chujo, Kazuo Nishiyama, Hirofumi Tachibana, Koji Yamada

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Abstract

Conjugated linoleic acid (CLA) is a powerful anti-carcinogenic fatty acid. Previously, we showed that 10trans 12cis (10t, 12c) CLA induced apoptotic cell death in rat hepatoma. Here, we demonstrated significant cytotoxic effects of 1 μM 10t, 12c-CLA, but not 9c, 11t-CLA, on dRLh-84 rat hepatoma cells. 9t, 11t and 9c, 11c-CLA also showed low levels of cytotoxic activity. 10t, 12c-CLA activated caspase-3, 9 followed by cytochrome c release from mitochondria into the cytosol. Inhibitors of caspase-3, 9 blocked the cytotoxicity of 10t, 12c-CLA. 10t, 12c-CLA also induced translocation of Bax protein into the mitochondrial membrane and cleavage of Bid protein. Lysosomal destabilization induced by 10t, 12c-CLA was observed by monitoring the re-localization of Acridine Orange and the leakage of β-hexosaminidase from lysosomes. 10t, 12c-CLA directly degraded the isolated lysosomes from the rat liver. Our observations indicate that 10t, 12c-CLA induces mitochondria-related apoptosis accompanied by lysosomal destabilization in rat hepatoma cells.

Original languageEnglish
Pages (from-to)176-184
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1735
Issue number3
DOIs
Publication statusPublished - Aug 15 2005

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Conjugated Linoleic Acids
Hepatocellular Carcinoma
Mitochondria
Apoptosis
Caspase 9
Lysosomes
Caspase 3
BH3 Interacting Domain Death Agonist Protein
trans-10,cis-12-conjugated linoleic acid
Hexosaminidases
bcl-2-Associated X Protein
Acridine Orange
Mitochondrial Membranes
Cytochromes c
Cytosol
Cell Death
Fatty Acids

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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Trans 10, cis 12-conjugated linoleic acid induces mitochondria-related apoptosis and lysosomal destabilization in rat hepatoma cells. / Yamasaki, Masao; Miyamoto, Yumi; Chujo, Hitomi; Nishiyama, Kazuo; Tachibana, Hirofumi; Yamada, Koji.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1735, No. 3, 15.08.2005, p. 176-184.

Research output: Contribution to journalArticle

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