Laboratory Study
Eye (2008) 22, 454–460; doi:10.1038/sj.eye.6702764; published online 16 March 2007
Beta-lapachone inhibits proliferation and induces apoptosis in retinoblastoma cell lines
None of the authors have any commercial or proprietary interest in any of the materials used in this study
H R Shah1, R M Conway1,2, K R Van Quill1, M C Madigan2, S A Howard1, J Qi1, V Weinberg3 and J M O'Brien1
- 1Ocular Oncology Unit, Department of Ophthalmology, University of California at San Francisco, San Francisco, CA, USA
- 2Save Sight Institute and Sydney Eye Hospital, University of Sydney, Sydney, New South Wales, Australia
- 3Comprehensive Cancer Center Biostatistics Core, University of California at San Francisco, San Francisco, CA, USA
Correspondence: JM O'Brien, Ocular Oncology Unit, UCSF Department of Ophthalmology, University of California at San Francisco, 10 Koret Way, Box 0730, San Francisco, CA 94143, USA. Tel: +1 415 476 0779; Fax: +1 415 476 0336; E-mail: aleja@itsa.ucsf.edu
Received 16 November 2006; Accepted 16 January 2007; Published online 16 March 2007.
Abstract
Aims
To investigate the cytotoxicity of beta-lapachone, a potent agent that may selectively target tumour cells, in retinoblastoma (RB) cell lines.
Methods
Growth inhibitory effects of beta-lapachone were evaluated in Y79, WERI-RB1, and RBM human retinoblastoma cell lines. Pro-apoptotic effects of beta-lapachone were evaluated in Y79 cells by detection of caspase 3/7 activity, by enzyme-linked immunosorbent assay for nucleosome fragments, and by cellular morphological analysis.
Results
Beta-lapachone induced significant dose-dependent growth inhibitory effects in all three retinoblastoma cell lines. The 50% growth inhibitory concentration (IC50) of this agent was 1.9 
M in Y79 cells, 1.3 M in WERI-RB1 cells, and 0.9 M in RBM cells. Beta-lapachone also induced proapoptotic effects in RB cells. Treatment of Y79 cells with 1.9 M beta-lapachone (IC50) resulted in a peak, fourfold induction of caspase 3/7 activity at 72 h post-treatment; a peak, 5.6-fold increase in nucleosome fragments at 96 h post-treatment; and a peak, 1.7-fold increase in the frequency of apoptotic cells at 48 h post-treatment, relative to vehicle-treated controls.
Conclusion
Beta-lapachone induced potent cytotoxic effects in RB cell lines at low micromolar concentrations, suggesting this agent could be useful in the clinical management of RB.
Keywords:
retinoblastoma, beta-lapachone, drug evaluation, preclinical, cell lines
