Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Comparative evaluation of the treatment efficacy of suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer cell lines and primary ovarian cancer cells from patients

Jürgen Sonnemann1, Jennifer Gänge1, Sabine Pilz1, Christine Stötzer2, Ralf Ohlinger3, Antje Belau3, Gerd Lorenz4 and James F Beck2*

Author Affiliations

1 Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Friedrich-Loeffler-Str. 23d, D-17487 Greifswald, Germany

2 Department of Paediatric Oncology/Haematology, Ernst Moritz Arndt University, Soldmannstr. 15, D-17487 Greifswald, Germany

3 Department of Obstetrics and Gynaecology, Ernst Moritz Arndt University, Wollweberstr. 1, D-17475 Greifswald, Germany

4 Department of Pathology, Ernst Moritz Arndt University, Friedrich-Loeffler-Str. 23e, D-17487 Greifswald, Germany

For all author emails, please log on.

BMC Cancer 2006, 6:183  doi:10.1186/1471-2407-6-183

Published: 11 July 2006

Abstract

Background

In most patients with ovarian cancer, diagnosis occurs after the tumour has disseminated beyond the ovaries. In these cases, post-surgical taxane/platinum combination chemotherapy is the "gold standard". However, most of the patients experience disease relapse and eventually die due to the emergence of chemotherapy resistance. Histone deacetylase inhibitors are novel anticancer agents that hold promise to improve patient outcome.

Methods

We compared a prototypic histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), and paclitaxel for their treatment efficacy in ovarian cancer cell lines and in primary patient-derived ovarian cancer cells. The primary cancer cells were isolated from malignant ascites collected from five patients with stage III ovarian carcinomas. Cytotoxic activities were evaluated by Alamar Blue assay and by caspase-3 activation. The ability of SAHA to kill drug-resistant 2780AD cells was also assessed.

Results

By employing the cell lines OVCAR-3, SK-OV-3, and A2780, we established SAHA at concentrations of 1 to 20 μM to be as efficient in inducing cell death as paclitaxel at concentrations of 3 to 300 nM. Consequently, we treated the patient-derived cancer cells with these doses of the drugs. All five isolates were sensitive to SAHA, with cell killing ranging from 21% to 63% after a 72-h exposure to 20 μM SAHA, while four of them were resistant to paclitaxel (i.e., <10% cell death at 300 nM paclitaxel for 72 hours). Likewise, treatment with SAHA led to an increase in caspase-3 activity in all five isolates, whereas treatment with paclitaxel had no effect on caspase-3 activity in three of them. 2780AD cells were responsive to SAHA but resistant to paclitaxel.

Conclusion

These ex vivo findings raise the possibility that SAHA may prove effective in the treatment of paclitaxel-resistant ovarian cancer in vivo.