Numerous natural and synthetic
quinone compounds possess significant antitumor properties. Various mechanisms have been proposed to account for these properties, including scission and degradation of
tumor cell
DNA, intracellular "redox cycling" to cogenerate semiquinone
free radicals and
reactive oxygen intermediates, and the interaction of
semiquinone radicals with
tumor cell surface flavoenzymes. However, no evidence has been presented to explain adequately the preferential attack on
tumor cells by
semiquinone radicals, as opposed to normal cells. To address this question, a synergistic interaction was examined. A
therapy consisting of a mixture of L-ascorbate and
2,6-dimethoxy-p-benzoquinone, was used for in vivo evaluation. BALB/c mice were depleted of functional T-lymphocytes by xenogeneic
monoclonal antibody pretreatment, challenged with
Ehrlich ascites tumor, and administered the semiquinone radical-generating
therapy. Mice depleted of CD4+ T-lymphocytes responded with rapidly fatal
tumor progression, with significantly decreased mean survival times over controls, whereas less severe responses were observed in mice devoid of CD8+ T-lymphocytes. Mice depleted of both T-lymphocyte subpopulations responded with uninhibited
tumor growth and rapid mortalities. When
tumor challenge occurred after
therapy,
tumor growth was significantly delayed in mice enriched for CD4+ T-lymphocytes, with demonstrable increases in mean survival time over controls. This
reagent combination had no significant effect on T-lymphocyte profiles in secondary lymphoid organs. These data suggest a synergistic phenomenon of semiquinone radical-induced cytostasis coupled with T-lymphocyte helper activity for optimal
tumor suppression.