title: Vitamin C enhances anticancer activity in methotrexate‑treated Hep3B hepatocellular carcinoma cells.
abstract: Methotrexate (MTX) has been widely used for rheumatoid arthritis therapy for a long time. MTX is also used as an anticancer drug for various tumors. However, many studies have shown that high-dose MTX treatment for cancer therapy may cause liver and renal damage. Alhough the mechanisms involved in MTX-induced liver and renal damage require further research, many studies have indicated that MTX-induced cytotoxicity is associated with increases in oxidative stress and caspase activation. In order to reduce MTX-induced side-effects and increase anticancer efficiency, currently, combination treatments of low-dose MTX and other anticancer drugs are considered and applied for various tumor treatments. The present study showed that MTX induces increases in H2O2 levels and caspase-9/-3 activation leading to cell death in hepatocellular carcinoma Hep3B cells. Importantly, this study is the first to demonstrate that vitamin C can efficiently aid low-dose MTX in inducing cell death in Hep3B cells. Therefore, the present study provides a possible powerful therapeutic method for tumors using a combined treatment of vitamin C and low-dose MTX.
authors: Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan, R.O.C.
authors: Giou-Teng
authors: GT
authors: Yiang
authors: Division of Allergy-Immunology-Rheumatology, Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan 265, Taiwan, R.O.C.
authors: Pei-Lun
authors: PL
authors: Chou
authors: Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Shalu, Taichung 433, Taiwan, R.O.C.
authors: Yu-Ting
authors: YT
authors: Hung
authors: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C.
authors: Jen-Ni
authors: JN
authors: Chen
authors: Graduate Institute of Cancer Biology, and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Wei-Jung
authors: WJ
authors: Chang
authors: Graduate Institute of Cancer Biology, and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
authors: Yung-Luen
authors: YL
authors: Yu
authors: Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Shalu, Taichung 433, Taiwan, R.O.C.
authors: Chyou-Wei
authors: CW
authors: Wei
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D010100:Oxygen; D008727:Methotrexate