Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs

• DOI: 10.1007/s00280-010-1418-6
• Publication Date: 2010-08-07T07:10:02Z
• Authors: Anja Frömberg; Daniela Gutsch; Daniel Schulze; Claudia Vollbracht; Gabriele Weiss; Frank Czubayko; Achim Aigner
• Keywords: IC50

While the benefits of ascorbic acid (vitamin C, ascorbate) as an essential nutrient are well established, its effects on tumor cells and in treatment controversial. In particular, conflicting data exist whether ascorbate may increase cytotoxic antineoplastic drugs or rather exert adverse drug sensitivity during cancer treatment. Findings further obscured regarding distinction between dehydroascorbate (DHA). Thus, purpose this study was to evaluate directly compare efficacy compared DHA, analyse if at pharmacological concentrations affects agents prostate carcinoma cells. We (supplied 'Pascorbin® solution for injection') DHA cell viability, determine IC50 values various lines. At below IC50, proliferation cycle analysed. furthermore changes cellular towards cytostatic upon pre-treatment with ascorbate. demonstrate higher therapeutic over lines, independent line-specific differences sensitivity, identify extracellular generation H2O2 critical mechanism action. show that, addition pro-apoptotic described previously, already exerts anti-proliferative Those based interference cycle, namely by inducing a G0/G1 arrest. Pre-treatment leads increased Docetaxel, Epirubicin, Irinotecan 5-FU, but not Oxaliplatin Vinorelbin. For Docetaxel linear correlation sensitizing effect dosage is observed. The redox-active form vitamin ascorbate, shows These antitumor mainly action and, induction apoptosis, also include Furthermore, specifically enhances potency certain chemotherapeutics, which implicates benefit