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Oncol Rep. 2017 Apr;37(4):2177-2184. doi: 10.3892/or.2017.5439. Epub 2017 Feb 10.

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways.

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Department of Cardiac Surgery, Tungs' Taichung Metroharbor Hospital, Taichung 435, Taiwan, R.O.C.
Department of Nursing, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan, R.O.C.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan, R.O.C.
Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan, R.O.C.


Methotrexate (MTX) is widely used as both an anticancer and anti-rheumatoid arthritis drug. Although MTX has been used to inhibit the growth of many cancer cells, it cannot effectively inhibit growth of triple-negative breast cancer cells (TNBC cells). Vitamin C is an antioxidant that can prevent oxidative stress. In addition, vitamin C has been applied as adjunct treatment for growth inhibition of cancer cells. Recent studies indicated that combined treatment with vitamin C and MTX may inhibit MCF-7 and MDA-MB-231 breast cancer cell growth through G2/M elongation. However, the mechanisms remain unknown. The aim of the present study was to determine whether combined treatment with low-dose vitamin C and MTX inhibits TNBC cell growth and to investigate the mechanisms of vitamin C/MTX-induced cytotoxicity. Neither low-dose vitamin C alone nor MTX alone inhibited TNBC cell growth. However, combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.

[Indexed for MEDLINE]

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