Apoptosis

, Volume 12, Issue 1, pp 113–123 | Cite as

Increased ROS generation and p53 activation in α-lipoic acid-induced apoptosis of hepatoma cells

  • G. Simbula
  • A. Columbano
  • G. M. Ledda-Columbano
  • L. Sanna
  • M. Deidda
  • A. Diana
  • M. Pibiri
Article

Abstract

α-lipoic acid (α-LA) is an antioxidant used for the treatment of a variety of diseases, including liver cirrhosis, heavy metal poisoining, and diabetic polyneuropathy. In addition to its protective effect against oxidative stress, α-LA induces apoptosis in different cancer cells types. However, whether α-LA acid induces apoptosis of hepatoma cells is unknown. Herein, we investigated whether α-LA induces apoptosis in two different hepatoma cell lines FaO and HepG2. The results showed that α-LA inhibits the growth of both cell lines as indicated by the reduction in cell number, the reduced expression of cyclin A and the increased levels of the cyclin/CDKs inhibitors, p27Kip1 and p21Cip1. Cell cycle arrest was associated with cell loss, and DNA laddering indicative of apoptosis. Apoptosis was preceded by increased generation of reactive oxygen species, and associated with p53 activation, increased expression of Bax, release of cytochrome c from mitochondria, caspases activation, decreased levels of survivin, induction of pro-apoptotic signaling (i.e JNK) and inhibition of anti-apoptotic signaling (i.e. PKB/Akt) pathways. In conclusion, this study provides evidence that α-LA induces apoptosis in hepatoma cells, describes a possible sequence of molecular events underlying its lethal effect, and suggests that it may prove useful in liver cancer therapy.

Keywords

Apoptosis p53 phosphorylation α-lipoic acid ROS Hepatoma cells 

Abbreviations

α-LA

α-lipoic acid

PARP

poly(ADP-ribose)polymerase

JNK

c-jun N-terminal kinase

PKB/Akt

protein kinase B/Akt

DCFH-DA

dichlorofluorescein diacetate

ROS

reactive oxygen species

NAC

N-acetyl-L-cysteine

Vit C

Vitamin C

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • G. Simbula
    • 1
  • A. Columbano
    • 1
  • G. M. Ledda-Columbano
    • 1
  • L. Sanna
    • 1
  • M. Deidda
    • 1
  • A. Diana
    • 2
  • M. Pibiri
    • 1
  1. 1.Department of ToxicologyOncology and Molecular Pathology UnitItaly
  2. 2.Department of CytomorphologyUniversity of CagliariItaly

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