Low doses of ascorbic acid modulate the effect of chemotherapy agents in sarcoma 180 tumor-bearing mice

Despite recent advances in cancer treatment, classical chemotherapy is still used as first-line treatment for a variety of tumors. However, the side effects associated with it are a relevant problem and one of the main reasons for discontinuation of cancer treatment. In this sense, antioxidants are widely used to reduce the side effects associated with chemotherapy, but little is known about their possible antagonistic effects. Therefore, this study aims to investigate the modulation of cisplatin (CDDP) and 5-fluorouracil (5-FU) by ascorbic acid (AA) in mice transplanted with sarcoma 180. A solid tumor was induced in the axillary region of Swiss mice (Mus musculus) and treated with isolated CDDP or 5-FU (5mg/kg) or in combination with low-dose AA (3.5 mg/kg / 17.5 mg/kg). To determine treatment efficacy, hematological and biochemical markers, as well as tumor and organ size were measured. The comet assay was used to assess genotoxicity in femoral bone marrow cells. The results demonstrated that tumor reduction was lower in the animals treated with the combination of 5-FU/CDDP with AA than in the groups receiving only the drugs. The comet assay demonstrated that CDDP/5-FU in combination with AA greatly reduced genotoxicity in bone marrow cells. It is hypothesized that the modulating effect of AA is due to its antioxidant activity, which influences the efficacy of chemotherapeutic drugs. The results show that the AA intake in combination with conventional chemotherapy leads to reduced treatment efficacy in animal models, warranting further studies on nutritional supplementation for cancer patients.