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

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.

Anti-cancer therapeutic benefit of red guava extracts as a potential therapy in combination with doxorubicin or targeted therapy for triple-negative breast cancer cells

“…About 15−20% of breast cancer occurrences are triple-negative breast cancer (TNBC) [15]. TNBC lacks estrogen receptors (ERs), progesterone receptors (PRs) and epidermal growth factor receptor 2 (HER2), and, therefore, chemotherapy, hormone therapy and targeted therapy are not useful for TNBC treatment [16][17][18]. Thus the development of a method for treating TNBC is important.…”

Effects of Ascorbic Acid, Dehydroascorbic Acid and Methotrexate on Breast Cancer Cell Viability

“…AA was also reported to be more toxic to cancer cells compared with normal cells, though the reasons behind this selectivity is not clear [28][29][30]. Studies have shown AA can lower the side effects caused by neoplastic drugs by enhancing their cytotoxicity, resulting in lower dosage of these drugs being used for cancer treatment [14][15][16][17]. In this study, the cytotoxicity of MTX, AA and DHA were tested for each compound using 231 cells.…”

“…There is longstanding interest in the potential anticancer effects of ascorbic acid (AA), which is a nutrient and a well-known antioxidant [11,12,13,14,15]. Vitamin C had anti-proliferative activity [13], and could enhance effects of doxorubicin, cisplatin and paclitaxel [14], mitoxantrone [15], and methotrexate [16,17]. Other studies however, suggested that AA might antagonize antineoplastic drugs leading to reductions in effectiveness [18].…”

Quimioterapia, Hormonioterapia E Novas Alternativas De Tratamento Do Adenocarcinoma Mamário

“…Juntamente com o 5-fluorouracil, é considerado um fármaco antimetabólito, pois atua na síntese de ácidos nucléicos e inibição de reações enzimáticas (JOSHI et al, 2017). São quimioterápicos ciclo-celular específicos e agem na fase S do ciclo por ação metabólica, ao promover bloqueio na síntese de DNA (WU et al, 1899).…”