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

3.5. Allium sativum L.

Allium sativum, commonly known as garlic, presents different biologically useful secondary metabolites with high sulphur content, such as S-allyl-cysteine, diallyl disulphide, diallyl trisulfide, and methyl allyl trisulfide [258]. Garlic also contains other beneficial compounds such as arginine, oligosaccharides, flavonoids, and selenium (i.e., cellular antioxidants) [259]. The main active ingredients of garlic, organic sulphur compounds, have attracted great attention as cancer prevention and treatment agents in breast cancer [260–263]. Among these constituents derived from garlic, the oil-soluble compounds are more effective than water-soluble compounds in suppressing breast cancer [264]. The mechanisms involved in the anticancer effect of garlic-containing compounds include activation of metabolizing enzymes that detoxify chemical carcinogens, inhibition of DNA adduct formation, suppression of reactive oxygen species production, induction of apoptosis, and regulation of cell cycle progression and signal transduction modification [264]. All referred to studies used experimental breast cancer cell lines, other studies extended their anticancer evidences to in vivomodels [265, 266], and no clinical trials are available in literature. For example, Liu et al. [260] demonstrated that diallyl trisulfide, a natural organosulphuric compound with most sulphur atoms found in garlic, suppressed the migration and invasion of breast cancer cell lines (MDA-MB-231 cells and HS 578t cells) and suggested that the inhibitory effects are associated with downregulation of the transcriptional activities of nuclear factor-kappa (NF-κB, a transcription factor that regulates the expression of antiapoptotic proteins) and ERK/MAPK (i.e., major kinases involved in cell survival) signalling pathways. In many malignant tumours, constitutive NF-activation occurs and consequently inflammation, proliferation, resistant to apoptosis, invasion, and so forth [267]. These authors reported that a concentration of diallyl trisulfide equal to 10 µM should be achieved in vivo for preventing or treating breast cancer. Chandra-Kuntal and collaborators established the critical role for reactive oxygen species in the anticancer effects of diallyl trisulfide compound using human breast cancer cells (MCF-7 and MDA-MB-231). Using an oestrogen receptor-negative human breast cancer cell line (MDA-MB-231), Nakagawa et al. [266] reported that diallyl disulphide synergizes the effect of eicosapentaenoic acid, a breast cancer suppressor, and antagonizes the effect of linoleic acid, a potent breast cancer stimulator. Diallyl trisulfide inhibits the expression of ADAM10 and ADAM17 (proteases with a role on metabolism of abnormal cells and whose high expression is associated with a lower disease-free survival in breast cancer patients) in estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells and seems to promote growth inhibition of breast cancer cells [268].

In terms of the cancer prevention, Wargovich et al. demonstrated robust chemopreventive action of constituents of garlic against experimentally induced cancer, including the mammary gland [32].

Despite garlic affecting cytochrome P450 3A4 activity, Cox et al. showed that garlic supplementation does not significantly affect the disposition of docetaxel but it can decrease the clearance of docetaxel in patients carrying a CYP3A51A allele (present in all African American) [58].

A case-control study performed in northwest Iran aimed to find the association between dietary Alliumconsumption and risk of breast cancer. The study included 285 women (25–65 years old) diagnosed with histopathologically confirmed breast cancer (grade II or III or clinical stage II or III) which completed a food-frequency validated questionnaire. A reduced risk of breast cancer associated with higher consumption of garlic and leek and an increased risk associated with high consumption of cooked onion was found [57].

No interactions are reported. Theoretically, garlic can increase bleeding with anticoagulants, aspirin, and antiplatelet drugs [269].