Ascorbic acid and its pro-oxidant activity as a therapy for tumours of oral cavity - A systematic review

Background: Ascorbic acid or Vitamin C is a potent dietary antioxidant with a double faced character, in that it exhibits a pro-oxidant activity arising from its routine antioxidant property that generates reactive free radicals, which induce cytotoxic effects at pharmacologic concentrations. A systematic review of this effect of ascorbic acid in the oral tumours and normal oral tissues would clearly elucidate the merits or demerits of employing vitamin C in treating the same. Objective: The aim of our systematic review is to critically review the studies reported in literature that have studied the pro-oxidant activity of ascorbic acid as a therapeutic option for treatment of oral neoplasms and its effects on normal oral cells. Methods: Articles were searched in PUBMED, MEDLINE using appropriate key words like "ascorbic acid", "pro-oxidant activity", "treatment", "oral neoplasms". Hand search of Journals was also performed. Articles were reviewed and analysed. Results: The search strategy included 17 potentially relevant articles for review of which, 12 were in vitro studies; 3 were in vivo animal studies; 1 was in vivo human study and 1 was ex vivo human study. The optimum concentration of ascorbic acid used to produce potential pro-oxidant associated cytotoxic effects was found to be 3-5 mM in vitro, 0.88-5 mM in vivo animals, 0.5-2 mM ex vivo in humans, and the corresponding effects are induction of apoptosis (caspase activation), necrosis, free radical formation, H2O2 generation, and DNA fragmentation. In contrast, the same pro-oxidant concentrations had no effect on the normal cells. Conclusion: The results of our systematic review show that the pro-oxidant activity of pharmacologic ascorbic acid is a part of its dose-dependent bimodal activity and is a result of the proposed Fenton mechanism. In vitro, animal and ex vivo studies of pharmacologic ascorbic acid (AA) have yielded meritorious results proving vitamin C as an effective cytotoxic agent against oral neoplastic cells with potentially no harming effects on normal cells. However, a shortage of clinical trials and in vivo human studies pertaining to evaluation of anti-tumour activity of vitamin C in tumours of oral cavity remains a lacuna in concluding ascorbic acid as a beneficial therapeutic option in treatment of oral neoplasms. (C) 2013 Elsevier Ltd. All rights reserved.