期刊
ONCOLOGY REPORTS
卷 37, 期 4, 页码 2177-2184出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2017.5439
关键词
vitamin C; methotrexate; triple-negative breast cancer cells; H2O2; caspase-3
类别
资金
- Ministry of Science and Technology, Taiwan [MOST103 2320-B-039052-MY3, MOST104-2321-B-039-005]
- Ministry of Health and Welfare, Taiwan [MOHW104-TDU-B-212-124-002]
- Taipei Tzu ChiHospital, Taiwan [TCRD-TPE-104-06, TCRD-TPE-104-34, TCRD-TPE-105-20, TCRD-TPE-105-02]
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 H2O, levels and activated both caspase-3 and p38 cell death pathways.
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