TITLE:
Megadoses of Sodium Ascorbate Efficiently Kill HL60 Cells in Vitro: Comparison with Arsenic Trioxide
AUTHORS:
Domenico Mastrangelo, Lauretta Massai, Giuseppe Fioritoni, Antonio Iacone, Paolo Di Bartolomeo, Patrizia Accorsi, Tiziana Bonfini, Michela Muscettola, Giovanni Grasso
KEYWORDS:
HL60; Acute Promyelocytic Leukemia; High Doses of Ascorbate; Cell Count and Viability Assays
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.8,
October
29,
2013
ABSTRACT:
Arsenic
Trioxide (ATO) is widely acknowledged as the treatment of choice for Acute
Promyelocytic Leukemia (APL). It is a “two-sided” drug since it can induce
differentiation or kill APL and other tumor cells according to the dosage. Part
of the cytotoxic effects of ATO on APL cells is due to its pro-oxidant
activity, a characteristic which ATO shares with a number of other compounds,
including high doses of ascorbate (ASC). In a comparative investigation on the
cytotoxic effects of both ATO and ASC on HL60 (APL) cell lines, in Vitro, we have been able to confirm
the known cytotoxic effects of ATO, but, more importantly, we have demonstrated
that ASC is significantly more effective than ATO, in killing these cancer
cells in Vitro, when the
concentrations are maintained within the millimolar (mM) range, i.e. the range of plasma concentrations
at which ASC induces oxidative damage to tumor cells. Since these plasma levels
can be reached only by the intravenous administration of high doses of ASC, we
propose that intravenous high doses of ASC may represent a potentially
revolutionary new approach in the management of APL.