Antitumor and analgesic activity of sinningia reitzii compounds in breast cancer models

BACKGROUND: Breast cancer is the most frequent in women for both cases and deaths and at least half of patients report pain as a symptom. A previous phytochemical study with the tubers of the Sinningia reitzii (Hoehne) L.E.Skog (SR) led to the isolation of 8 naphthoquinones. Among them, the 6,7-dimethoxydunnione (SR4) showed antitumor activity in vitro. This study aimed to evaluate the antitumor and analgesic potential of SR components against Ehrlich carcinoma in Swiss female mice, and in MCF-7 and HB4a breast cell lineages. METHODS: Mice were inoculated with tumor cells and treated daily with SR extract, namely dichloromethane fraction (ESR, 10, 30 and 100 mg kg− 1), SR4 (3 mg kg− 1) or vehicle, orally; or with the methotrexate chemotherapy (2.5 mg kg− 1) via i.p., every 3 days, along 21 days. RESULTS: Both ESR and SR4 induced toxicity in the tumor cell MCF-7 but did not in non-tumor human breast cell HB4a in culture. ESR and SR4 showed antitumor effects, but ESR showed more expressive results. The ESR caused changes in the oxidative balance in the tumor tissue and decreased myeloperoxidase levels without reducing the levels of pro-inflammatory cytokines. ESR induced necrosis in tumor and increased the gene expression of Ripk1, which is involved in the necroptosis pathway. In addition, ESR showed acute, but not cumulative, analgesic effect in pain associated with Ehrlich cells inoculation in the mice paw. CONCLUSIONS: The components of Sinningia reitzii, mainly the ESR, are promising sources of drugs that combine analgesic and antitumor effects, without systemic toxicity.