title: Molecular mechanisms of pharmacological doses of ascorbate on cancer cells.
abstract: Intravenous application of high-dose ascorbate (vitamin C) has been used in complementary medicine since the 1970s to treat cancer patients. In recent years it became evident that high-dose ascorbate in the millimolar range bears selective cytotoxic effects on cancer cells in vitro and in vivo. This anticancer effect is dose dependent, catalyzed by serum components and mediated by reactive oxygen species and ascorbyl radicals, making ascorbate a pro-oxidative pro-drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. It further depends on HIF-1 signaling and oxygen pressure, and shows a strong epigenetic signature (alteration of DNA-methylation and induction of tumor-suppressing microRNAs in cancer cells). The detailed understanding of ascorbate-induced antiproliferative molecular mechanisms warrants in-depth preclinical evaluation in cancer-bearing animal models for the optimization of an efficacious therapy regimen (e.g., combination with hyperbaric oxygen or O2-sensitizers) that subsequently need to be evaluated in clinical trials.
authors.affiliation: Department of Internal Medicine I, Medical University Hospital, Tuebingen, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Venturelli
authors.forename: Tobias W
authors.initials: TW
authors.lastname: Sinnberg
authors.forename: Heike
authors.initials: H
authors.lastname: Niessner
authors.forename: Christian
authors.initials: C
authors.lastname: Busch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003131:Combined Modality Therapy; D000529:Complementary Therapies / Q000331:legislation & jurisprudence; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval / Q000331:legislation & jurisprudence; D044127:Epigenesis, Genetic / Q000187:drug effects; D005062:European Union; D006801:Humans; D007262:Infusions, Intravenous; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics; D008517:Phytotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012308:Risk Management / Q000331:legislation & jurisprudence; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D001205:Ascorbic Acid