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Oncol Rep. 2014 Sep;32(3):1057-63. doi: 10.3892/or.2014.3289. Epub 2014 Jun 25.

Vitamin C enhances anticancer activity in methotrexate‑treated Hep3B hepatocellular carcinoma cells.

Author information

1
Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan, R.O.C.
2
Division of Allergy-Immunology-Rheumatology, Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan 265, Taiwan, R.O.C.
3
Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Shalu, Taichung 433, Taiwan, R.O.C.
4
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C.
5
Graduate Institute of Cancer Biology, and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.

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.

PMID:
24969544
PMCID:
PMC4121419
DOI:
10.3892/or.2014.3289
[Indexed for MEDLINE]
Free PMC Article

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