Phytotherapy and Nutritional Supplements on Breast Cancer 用于乳腺癌治疗的植物疗法和营养补充剂

3.11. Mistletoe

Mistletoe (Viscum album from the Viscaceae family), as part of anthroposophical medicine, is potentially effective against cancer and is used frequently in breast cancer due to its minimal side effects and the fact that these side effects are not life threatening [363]. The mistletoe contains different types of biological active ingredients, but the main constituents responsible for anticancer and immunomodulatory effects are lectins (ML-I, ML-II, and ML-III) [364, 365].

Experiments in cell cultures, animal models, and clinical data propose that cytotoxic and antitumour activities of mistletoe may be mediated by different mechanisms: apoptosis induction and necrosis, cell cycle inhibition [366, 367], and activation of specific and nonspecific immune system [368, 369].

Different in vitro studies demonstrated the antiproliferative effect of mistletoe extract against breast cancer cell lines [370, 371]. Kelter et al. proved that mistletoe extracts have cytotoxic activity on different human breast cancer cell lines and suggested that no growth stimulation of these cell occurred [370]. Using human breast carcinoma cell lines HCC 1937 and HCC 1143, Weissenstein and collaborators suggested that no herb-drug interactions occurred from the exposition of cancer cells simultaneously with doxorubicin (i.e., a chemotherapeutic) and Viscum album extract [371]. Additionally, at higher concentrations of mistletoe extract an additive in vitro inhibitory effect was observed. When Viscum album extract was associated with trastuzumab in an in vitro SK-BR-3 cells test, the results suggested no herb-drug interaction and exhibited a complementary anticancer effect [347]. A similar synergistic anticancer effect was observed in inhibition in the growth of both breast cancer cell lines (i.e., MCF-7—oestrogen receptor-positive—and MDA-MB 231-oestrogen receptor-negative) when the authors combined doxorubicin and lectin from Korean mistletoe [372]. Furthermore, in vivo investigations using different animal models were also presented in literature. For example, Beuth et al. reported the dose-dependent anticancer activity of mistletoe using a BALB/c mouse/BT474 ductal breast carcinoma model [373].

Several studies on breast cancer patients receiving chemotherapy report an efficacy on survival rate, tumour reduction and remission, and better quality of life with reduction of adverse reaction of standard chemotherapy when additionally treated with mistletoe products [84–87]. Safety and efficacy were set as the endpoints in a multicentric and comparative clinical trial conducted by Beuth et al. among women with primary breast cancer who received mistletoe extract [88]. In clinical trials, some limitations should also be pointed out such as limited sample size, lack of control, exclusion and inclusion criteria of the clinical trial, quality rating, and mistletoe preparations.

Twelve patients were selected by the presence of histological confirmed breast cancer tumour (≥2 cm in diameter) and included in a study to investigate the mistletoe effect in tumour regression of breast cancer. After six months, the mistletoe extract therapy demonstrated being highly effective [83].

Despite the promising results for the use of mistletoe in addition to chemotherapy, the discussion on the reduction of side effects and improvement of quality of life in breast cancer patients remains open and is still a controversial topic.