NEW YORK MAR 19, 2007 (Reuters Health) - At low micromolar concentrations, beta-lapachone, a natural compound derived from the bark of the South American lapacho tree, impedes the growth and proliferation and actively promotes apoptosis of cultured human retinoblastoma cells.
In the March 16th online issue of the journal Eye, researchers note that retinoblastoma is the most common primary intraocular malignancy of childhood, affecting 1 in 15,000 children. Although overall survival rates have been estimated to be as high as 95%, significant long-term morbidity and even secondary mortality have been associated with traditional therapy, which may involve chemotherapy and/or radiation.
Beta-lapachone is known to induce cytotoxic effects in a wide variety of malignant human cell types including colon, lung, prostate, breast, pancreatic, ovarian, and bone cancers, as well as some blood cancers.
Retinoblastoma may now be added to this list, according to Dr. Joan M. O"Brien of the University of California, San Francisco and colleagues, who observed that beta-lapachone induced significant dose-dependent growth inhibitory effects in three retinoblastoma cell lines.
The compound also had proapoptotic effects, as evidenced by significant post-treatment increases in caspase 3/7 activity by enzyme-linked immunosorbent assay for nucleosome fragments and in the frequency of apoptotic cells at 48 hours after treatment in retinoblastoma cells compared with vehicle-treated controls.
In summary, Dr. O"Brien and colleagues say the "potent cytotoxic effects of low doses of beta-lapachone in retinoblastoma cells observed in the present study and the recently reported high degree of sensitivity of beta-lapachone towards cancer cells in general suggest that beta-lapachone could have utility in the treatment of retinoblastoma."
The team is currently conducting in vivo studies in a transgenic murine model of retinoblastoma to better evaluate efficacy and toxicity of beta-lapachone.
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