Objectives: To tests the sensitivity of Y79 retinoblastoma cell lines to high doses of ascorbate, in vitro, and compare
its effects with those of some chemotherapeutic agents routinely employed in the treatment of retinoblastoma.
Methods: Y79 retinoblastoma cells have been exposed to increasing doses of either sodium ascorbate (SA) or
Melphalan (MEL), to define a dose-response curve around the peak plasma concentrations reached by both chemicals
when administered according to the existing therapeutic procedures and protocols. The assessment of cell number and
viability was performed, before and after exposure, with both the manual (Trypan Blue Exclusion Test) and automated
(flow cytometry) methods. Fluorescence microscopy and direct observation of cells in culture, with inverted microscope,
were also performed.
Results: Y79 cells are highly sensitive to the cytotoxic effect of SA, with cell viability reduced of over 90% in some
experiments. As reported in the literature, this effect is directly cytotoxic and most probably mediated by acute oxidative
stress on different cellular components. The same does not apply to Melphalan which, at the doses commonly used for
therapeutic purposes, did not show any significant effect on cell viability, in vitro.
Conclusion: To our knowledge, this is the first report showing that high doses of SA can actively kill retinoblastoma
cells in vitro. While it is not surprising for SA, to show direct cytotoxic effect on tumor cells, the data reported herein
represent the first evidence in favor of the possible clinical use of high doses of intravenous SA, to treat children
affected by retinoblastoma. Given the many advantages of SA over the chemotherapeutic agents commonly employed
to treat cancer (including its almost total absence of toxic or side effects, and its exclusive specificity for cancer cells),
it is reasonable to assume, from the data reported herein, that the high doses of intravenous ascorbate, have the
potential to represent a real revolution in the treatment of retinoblastoma
