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

  • Authors:
    • Ching-Wen Wu
    • Hsiao-Chun Liu
    • Yung-Luen Yu
    • Yu-Ting Hung
    • Chyou-Wei Wei
    • Giou-Teng Yiang
  • View Affiliations

  • Published online on: February 10, 2017     https://doi.org/10.3892/or.2017.5439
  • Pages: 2177-2184
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Abstract

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.
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April-2017
Volume 37 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wu C, Liu H, Yu Y, Hung Y, Wei C and Yiang G: 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. Oncol Rep 37: 2177-2184, 2017
APA
Wu, C., Liu, H., Yu, Y., Hung, Y., Wei, C., & Yiang, G. (2017). 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. Oncology Reports, 37, 2177-2184. https://doi.org/10.3892/or.2017.5439
MLA
Wu, C., Liu, H., Yu, Y., Hung, Y., Wei, C., Yiang, G."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". Oncology Reports 37.4 (2017): 2177-2184.
Chicago
Wu, C., Liu, H., Yu, Y., Hung, Y., Wei, C., Yiang, G."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". Oncology Reports 37, no. 4 (2017): 2177-2184. https://doi.org/10.3892/or.2017.5439