Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway

Shi, Dong-yun; Liu, Hong-lei; Stern, Jeremy S.; Yu, Pei-zhong; Liu, Shan-lin

doi:10.1016/j.febslet.2008.04.021

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Volume 582, Issue 12 , Pages 1667-1671, 28 May 2008

Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway

Edited by Vladimir Skulachev

Dong-yun Shi
- Department of Biochemistry, Shanghai Medical College of Fudan University, Free Radical Research Center of Fudan University, Shanghai 200032, PR China
- Pharmaceutical Science Research Division, School of Health and Life Sciences, King’s College London, London SE1 9NH, UK
- Corresponding authors. Address: Department of Biochemistry, Shanghai Medical College of Fudan University, Free Radical Research Center of Fudan University, Shanghai 200032, PR China. Fax: +86 21 54237299.
Hong-lei Liu
- Pharmaceutical Science Research Division, School of Health and Life Sciences, King’s College London, London SE1 9NH, UK
Jeremy S. Stern
- Department of Neurology, St. George’s Hospital, London SW17 0QT, UK
Pei-zhong Yu
- Department of Biochemistry, Shanghai Medical College of Fudan University, Free Radical Research Center of Fudan University, Shanghai 200032, PR China
Shan-lin Liu
- Department of Biochemistry, Shanghai Medical College of Fudan University, Free Radical Research Center of Fudan University, Shanghai 200032, PR China
- Corresponding authors. Address: Department of Biochemistry, Shanghai Medical College of Fudan University, Free Radical Research Center of Fudan University, Shanghai 200032, PR China. Fax: +86 21 54237299.

Received 4 March 2008; received in revised form 31 March 2008; accepted 11 April 2008. published online 22 April 2008.

Abstract

We report here that alpha-lipoic acid (α-LA), a naturally-occurring antioxidant, scavenges reactive oxygen species (ROS) followed by an increase in apoptosis of human hepatoma cells. Apoptosis induced by α-LA was dependent upon the activation of the caspase cascade and the mitochondrial death pathway. α-LA induced increases in caspase-9 and caspase-3 but had no significant effect on caspase-8 activity. Apoptosis induced by α-LA was found to be mediated through the tensin homologue deleted on chromosome 10 (PTEN)/Akt pathway. Prior to cell apoptosis, PTEN was activated and its downstream target Akt was inhibited. Our findings indicate that increasing ROS scavenging could be a therapeutic strategy to treat cancer.

Abbreviations: α-LA, α-lipoic acid, DCFH-DA, dichlorofluorescein diacetate, DHLA, dihydrolipoic acid, PI3K, phosphoinositide 3-kinase, PtdIns(3,4,5)P₃, phosphatidyl inositol-3,4,5-triphosphate, PtdIns(4,5)P₃, phosphatidyl inositol-4,5-triphosphate, PKB/Akt, protein kinase B/Akt, PTEN, tensin homologue deleted on chromosome 10, ROS, reactive oxygen species, TUNEL, terminal deoxynucleotidyl transferase mediated dUTP Nick End Labelling