Abstract

Mistletoes are hemi-parasitic plants widely distributed around the world, used in folk medicine to treat many diseases including diabetes, hypertension, menopausal syndrome and as complementary or adjuvant treatment for cancer. The objective of the present work was the evaluation of oestrogenic activity of hydromethanolic extract of mistletoe Struthanthus venetus dried leaves (StvHME), to evaluate its potential benefits in menopause and breast cancer, which have not been reported so far. Uterotrophic activity was evaluated in immature female CD1 mice, administering StvHME (10, 100 and 500 mg/kg) for three consecutive days compared to the natural hormone 17β-oestradiol (E2, 10 μg/kg). Comparison of the MCF-7 positive oestrogen receptor human breast adenocarcinoma cell proliferation in the presence of StvHME (0.5, 5 and 50 μg/ml) or E2 (10-12-10-10M) related to untreated control cells was assessed using MTT cell viability assay. StvHME, produced biphasic effects in mice uteri; low doses (10 mg/kg) decreased uterine weight (15-38%; p<0.05), while a higher dose (500 mg/kg) increased uterine weight (28-36%; p<0.05). StvHME concentrations tested inhibited MCF-7 cell proliferation, contrasting with E2 which increased it. StvHME (50 μg/ml) antagonized the proliferative response to E2 (10-12 to 10-10 M) behaving as an anti-oestrogen. The antiproliferative response of StvHME (50 μg/ml) showed synergism with the oestrogen antagonists Tamoxifen and Fulvestrant (ICI 182,780). Our results suggest the presence of oestrogenic and anti-oestrogenic components in the StvHME that could be acting through the oestrogen ERα and ERβ receptors. Therefore, StvHME has potential utility as a complementary therapy for breast cancer.

Key words: mistletoe, Struthanthus venetus, MCF-7 cells, oestrogenicity, anti-oestrogenic, anti-cancer, menopause.

Abbreviation

StvHME, hydro-methanolic extract from the mistletoe Struthanthus venetus dried leaves; E₂, 17β-oestradiol; MCF-7, Michigan Cancer Foundation-7; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ERα, oestrogenic receptor alpha; ERβ, oestrogenic receptor beta; ATCC; American Type Culture Collection; DMEM, phenol red-free Dulbecco’s modified Eagle’s medium; CDFBS, charcoal-dextran stripped foetal bovine bovine serum; EDTA, ethylendiaminetetra acetic acid; PBS, phosphate-buffered saline; OD, optical density; ANOVA, analysis of variance.