Cancer Letters
Volume 208, Issue 1 , Pages 51-58, 10 May 2004

Potentiated anticancer effects on hepatoma cells by the retinoid adapalene

Department of Internal Medicine I, University Erlangen-Nuernberg, Ulmenweg 18, D-91054 Erlangen, Germany

Received 11 July 2003; accepted 22 December 2003.

Abstract 

Retinoids can block cell proliferation and induce apoptosis in tumor cells. The antitumoral effect of synthetic retinoids like Adapalene (ADA) on hepatoma cells (HepG2, Hep1B) was investigated. Cell proliferation was assessed by measuring DNA synthesis and apoptosis by flow cytometry and immunocytochemistry. Cell cycle- and apoptosis-associated proteins were semi-quantified by Western Blotting and breakdown of mitochondrial membrane potentials was detected by JC-1 staining.

ADA at 10−4M efficiently induced apoptosis, reaching 61.7% in HepG2 and 79.1% in Hep1B after 72 h incubation. This was accompanied by up-regulation of pro-apoptotic bax and caspase 3, while bcl-2 was down-regulated, shifting the bax/bcl-2 ratio to >2.3 in hepatoma cells.

ADA inhibits hepatoma cell growth in vitro and is a powerful inducer of hepatoma cell apoptosis.

Keywords: Apoptosis, Hepatocellular carcinoma, Retinoic acid, Synthetic retinoid

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PII: S0304-3835(04)00057-6

doi:10.1016/j.canlet.2003.12.026

Cancer Letters
Volume 208, Issue 1 , Pages 51-58, 10 May 2004