Ascorbic acid kills Epstein-Barr virus positive Burkitt lymphoma cells and Epstein-Barr virus transformed B-cells in vitro, but not in vivo.
Ascorbic acid has been shown to kill various cancer cell lines at pharmacologic concentrations. We found that Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) cells were more susceptible to ascorbic acid-induced cell killing than EBV-negative BL cells or EBV-transformed lymphoblastoid cells (LCLs). Ascorbic acid did not induce apoptosis in any of the tested cells but did induce the production of reactive oxygen species and cell death. Previously, we showed that bortezomib, a proteasome inhibitor, induces cell death in LCLs and EBV-positive BL cells. We found that ascorbic acid is strongly antagonistic for bortezomib-induced cell death in LCLs and EBV-positive BL cells. Finally, ascorbic acid did not prolong survival of severe combined immunodefiency mice inoculated with LCLs either intraperitoneally or subcutaneously. Thus, while ascorbic acid was highly effective at killing EBV-positive BL cells and LCLs in vitro, it antagonized cell killing by bortezomib and was ineffective in an animal model.
Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Amber N
AN
Shatzer
Michael Graham
MG
Espey
Mayra
M
Chavez
Hongbin
H
Tu
Mark
M
Levine
Jeffrey I
JI
Cohen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000821:virology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D051379:Mice; D011719:Pyrazines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D017382:Reactive Oxygen Species; D000069286:Bortezomib; D001205:Ascorbic Acid