Abstract
Background: Breast cancer is one of the principal causes of death among women and there is a pressing need to develop novel and effective anti-cancer agents. Natural plant products have shown promising results as anti-cancer agents. Their effectiveness is reported as decreased toxicity in usage, along with safety and less recurrent resistances compared with hormonal targeting anti-cancer agents. Methods: A literature search was conducted for all English-language literature published prior to June 2020. The search was conducted using electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library. The search strategy included keywords such as breast cancer, herbs, anti-cancer biologically active components, clinical research, chemotherapy drugs amongst others. Results: The literature provides documented evidence of the chemo-preventative and chemotherapeutic properties of Ginseng, garlic (Allium sativum), Black cohosh (Actaea racemose), Tumeric (Curcuma longa), Camellia sinenis (green tea), Echinacea, Arctium (burdock), Flaxseed (Linum usitatissimum) and Black Cumin (Nigella sativa). Conclusions: The nine herbs displayed anti-cancer properties and their outcomes and mechanisms of action include inhibition of cell proliferation, angiogenesis and apoptosis as well as modulation of key intracellular pathways. However, more clinical trials and cohort human studies should be conducted to provide key evidence of their medical benefits.
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Key Points
There are studies that have provided evidence of the efficacy of natural products such as herbs in the development of anti-cancer drugs. This review is centered on the biochemical properties and pharmacokinetics of Ginseng, garlic (Allium sativum), Black cohosh (Actaea racemose), Tumeric (Curcuma longa), Camellia sinenis (green tea), Echinacea, Arctium (burdock), Flaxseed (Linum usitatissimum) and Black Cumin (Nigella sativa) which possess chemo-preventative and chemotherapeutic properties. These well-known herbs have been selected as they are commonly used in traditional medicine as adjuvants in breast cancer therapy and there is documentation of their mechanisms of action.
This review also examined the mechanism(s) of action and the modulatory role of these herbs of key intracellular signaling pathways involved in the development and progression of breast cancer. In addition, current limitations of these herbs, challenges and future directions for experimental in vitro and in vivo techniques, animal models and clinical research are critically appraised.
Flaxseed is a main plant source of essential fatty acids and its physico-composition includes: lignans, minerals such as magnesium, phosphorous and calcium, proteins such as globulins (linin and conlinin) and glutelin present in ratios of 80% to 20%, insoluble (cellulose and lignin) and soluble (mucilage gums) dietary fibers, and soluble polysaccharides and vitamins (A, C and E).
Flaxseed comprises approximately 800 times more lignans than other plants. They are bioactive, non-nutritional and phenolic compounds that are phytoestrogens and comprised predominantly of secoisolariciresinol diglucoside (SDG) (294–700 mg/100 g) which makes up approximately 95% of the lignin content with the remaining 5% consisting of lariciresinol (3.04 mg/100 g), pinoresinol (3.32 mg/100 g) and matairesinol (0.55 mg/100 g).
α-linolenic acid can be metabolized into eicosapentaenoic acid (EPA) (ω-3) and docosahexaenoic acid (DHA) (ω-3) and all three ω-3 fatty acids have been widely described in numerous conditions including: diabetes mellitus, neurological disorders, atherosclerosis, hypertension and cardiovascular disease. Experimental studies have investigated the anti-tumorigenic effect of flaxseed and some of these involved animals, where mice were injected with breast tumor cells.
Immuno-histochemical study revealed decreased expression of both epidermal growth factor receptor and insulin-like growth factor I. Flaxseed and its lignan, enterolactone, counteracted angiogenesis and ex-induced growth in mice inoculated with MCF-7 human breast cancer cells. The in vivo findings were confirmed in vitro as flaxseed and its lignans inhibited the secretion of vascular endothelial growth factor, which is an effective potent stimulator of angiogenesis. Conversely, secoisolariciresinol diglucoside, a lignin present in flaxseed, did not reduce breast tumor growth nor induce apoptosis in athymic mice.
There are studies that have investigated whether flaxseed augments or interferes with the effect of tamoxifen. In an in vivo study with athymic mice inoculated with MCF-7 breast cancer cells and implanted with an E2 pellet, flaxseed inhibited the growth of the tumor size by 74%, while both tamoxifen and flaxseed caused tumor regression by over 53%. It was observed that flaxseed at both high and low E2 levels augment the tumor-inhibited effects of tamoxifen. There have been a number of systematic reviews of the efficiency of flaxseed or its lignans in reducing breast cancer risk. In a review of 10 studies by Fower et al., flaxseed or secoisolariciresinol diglycoside consumed daily significantly decreased breast cancer risk via increased tumor apoptotic index, and reduced cell proliferation and HER2 expression.
In summary, experiments involving culture cells and tumor animal models showed that flaxseed exhibited anti-cancer properties as there was a reduction of tumor growth and increased apoptosis. There is a synergistic relationship between flaxseed and tamoxifen as the herb increases or maintains the efficacy of the chemotherapy drug. Clinical studies have concluded that flaxseed has the potential to decrease the risk, tumor growth and size in breast cancer patients.