Botanical Combo Shows Promise Against Breast Cancer

Breast Intraductal CarcinomaIntraductal carcinoma of the breast, showing central tumor necrosis and distended ductal structure, but intact basement membrane (Image: Medscape)A physician-formulated combination of Turmeric, Astragalus, and other botanical and mushroom-derived ingredients is showing promise as a potential natural therapy for women with breast cancer.

The formula contains standardized extracts of Turmeric (Curcuma longa (BCM-95)), Skullcap (Scutellaria barbata), and Astragalus membranaceus, along with Quercetin, Diindolylmethane (DIM), and a trio of medicinal mushrooms: Coriolus (Trametes versicolor); Reishi (Ganoderma lucidum), and the lesser-known Meshima (Phellinus linteus).

Individually, all of these herbs and fungi contain bioactive compounds showing anti-inflammatory, immunomodulatory, hormone regulatory, and anti-tumor effects in cell culture and animal studies. In some cases, there are early-stage human studies also suggesting that these herbs have potential benefit against certain forms of cancer, including breast cancer.

The combination was developed by Isaac Eliaz, MD, and EcoNugenics, a California-based company that specializes in development of innovative condition-specific, botanically-based nutraceuticals. With this formula—marketed as BreastDefend—Eliaz hoped to create synergy between the various herbs optimizing their myriad anti-cancer and immunostimulatory mechanisms.

BreastDefend is taken orally, two to four capsules per day. A full four-cap dose delivers 950 mg of the quercetin-scutellaria-curcumin-astragalus combination, plus 500 mg of the mushroom combo, and 200 mg of DIM.

Inhibiting Cell Proliferation

In a cell culture study, BreastDefend inhibited proliferation and metastatic behavior of a highly invasive form of human breast cancer that is “triple negative” for estrogen, progesterone receptor and HER2. In tissue culture experiments, the botanical combination inhibited cell proliferation and blunted invasiveness. Treated cells showed suppression of urokinase plasminogen activator (uPA), as well as downregulation of CXCR4 and other genes involved in tumor proliferation (Jiang J, et al. Integrative Cancer Therapies. 2010;10(2):192-200).

In a subsequent study of mice implanted with human metastatic breast cancer cells, the BreastDefend formula decreased incidence of breast-to-lung metastases by 70%. In the untreated control animals, 67% showed lung metastases; among the mice treated with the herbal combination that was reduced to 20% (Jiang J, et al. Oncology Reports. 2012;28:1139-45).

Recently published data indicate that the formula can sensitize estrogen receptor-positive human breast cancer cells to Tamoxifen, significantly enhancing apoptosis, suppressing tumor growth, and reducing tumor weight when compared Tamoxifen alone (Cheng S, et al, BMC Complementary Alternative Med. 2017;17(1):115).

Diverse Mechanisms

Though BreastDefend has not yet been subjected to a human clinical trial, the pre-clinical evidence is highly suggestive of potential benefit for preventing and treating various forms of breast cancer, alone and in combination with conventional therapies.

The combination of herbs and mushrooms in BreastDefend provides a very wide range of naturally occurring anti-tumor compounds that can:

  • Modify cytochrome P45 enzyme mediated hormone metabolism toward more favorable estrogen metabolites
  • Reduce inflammation
  • Normalize cell behavior
  • Induce apoptosis in breast cancer cells
  • Inhibit angiogenesis
  • Inhibit estrogen receptor stimulation
  • Normalize glucose metabolism
  • Stimulate immune system response
  • Promote detoxification of xenobiotic compounds

ScutellariaScutellaria barbata (Skullcap)Skullcap (Scutellaria barbata): This herb has been used for centuries in traditional Chinese medicine, as a support for immunity. Cell culture studies show it can inhibit proliferation of both ER-positive and ER-negative human breast cancer cells; induce apoptosis and G2 cycle arrest; and inhibit glycolysis and other metabolic pathways preferentially activated in tumor cells (Klawitter J, et al. Int J Cancer. 2011;129(12):2945-57; Perez AT, et al. Breast Can Res Treat. 2010:120(1)111-18; Fong S, et al. Cancer Biol Ther. 2008:7(4):577-86).

A multicenter Phase 1B clinical study of women with stage IV breast cancer showed Scutellaria barbata was a safe adjunct to conventional treatment (Perez, et al 2010). A second phase 1 trial, also of women with stage IV breast cancer, showed that Scutellaria barbata can induce tumor regression in some patients, while promoting tumor stability in others (Rugo H, et al. Breast Can Res Treat. 2007: 105(1):117-28).

Turmeric (Curcuma longa): One of the most widely studied herbs, turmeric exerts multiple antioxidant, apoptotic, antiflammatory, chemopreventive, chemosensitizing, and TurmericCurcuma longa (Turmeric)radiosensitizing effects. It downregulates NF-kB, STAT3, COX2, and other genes and molecular signals associated with inflammation and tumor growth, while simultaneously upregulating genes that inhibit tumor growth.

Both in vitro and in vivo, it has been shown to sensitize tumors to a range of different anti-cancer drugs.

Curcumin has been found to inhibit proliferation of various tumor cell lines in

culture prevent carcinogen-induced cancers in rodents and inhibit growth of human tumors in animal models. Phase I and II trials indicate that curcumin is very safe (Kunnumakkara AB, et al. Cancer Lett. 2008:269(2):199-225).

Astragalus rootAstragalus membranaceaeAstragalus: Widely used in Ayurvedic and traditional Chinese medicine, Astragalus enhances immune system function and promotes hematopoiesis. It is neuroprotective, hepatoprotective, and anti-inflammatory. It also normalizes glucose metabolism. In the cancer context, it shows direct and indirect antitumor activity.

Polysaccharides from Astragalus inhibit breast cancer cell lines. The herb has a unique ability to enhance T-cell activation without affecting B-cell proliferation (Wan CP, et al. Acta Pharmacol Sin. 2013:34(4):522-30). Much of its anti-neoplastic impact owes to its ability to enhance immune responses by increasing secretion of IL-2, IL-12, and Tumor Necrosis Factor-a while also reducing IL-10 (Yang B, et al. Int J Biol Macromol. 2013;62:287-90).

Quercetin: A flavonol found in many vegetables, quercetin has strong anti-inflammatory effects. In the cancer context, it promotes apoptosis, inhibits cell growth, favorably modulates signaling pathways, antagonizes estrogen receptors, and shifts CYP450 activity to favor production of 2-hydroxyestrone-- the “healthier” less carcinogenic form of estrogen (Mense SM, et al. J Steroid Biochem Mol Biol. 2008;110:157-62).

Quercetin inhibits proliferation in estrogen and progesterone receptor positive breast cancer cell lines. It induces apoptosis by modulating a number of cell signaling pathways. It also inhibits glucose uptake, and reduces tumor cell viability in ER-positive and negative breast cancer tissue (Chen FP et al. Climacteric. 2014;17(4):385-92.). There’s some indication that quercetin may act as an estrogen receptor antagonist (Resende FA, et al. PLoS One. 2013; 8(10):e74881.).

Diindolyl Methane (DIM): The most physiologically active metabolite of the glucosinolate compounds found in cruciferous vegetables, DIM also pushes estrogen metabolism toward production of 2-hydroxyestrone rather than the carcinogenic 16-hydroxyestrone metabolite.

DIM has shown growth limiting effects in a number of human cancers. It also has chemo-sensitization activity that helps reduce the toxicity of, and resistance to, conventional chemotherapeutic drugs (Ahmed A, et al. Curr Drug Targets. 2010;11(6):652-66)

DIM stops cell cycle progression of human breast cancer cells regardless of their estrogen dependence and p53 status, via modulation of specific cell cycle regulatory pathways (Jin Y, et al. Mol Cell Biochem. 2011;358:345-54).

Coriolus (Trametes versicolor); Reishi (Ganoderma lucidum) and Meshima (Phellinus linteus): The literature on each of these medicinal mushrooms is vast, and all have longCoriolus Coriolus (aka Trametes) versicolor histories of use in traditional Asian medicine.

Each contains compounds that affect multiple immune system signaling pathways, and potentiate anti-tumor responses via activation of cytotoxic macrophages, monocytes, neutrophils, natural killer cells, dendritic cells, and cytotoxic T-cells. These mushrooms also induce interleukins, interferon, and colony stimulating factors all of which have immunostimulatory effects.

Ganoderic acids extracted from Ganoderma lucidum can suppress growth, angiogenesis, and invasiveness of highly invasive and metastatic breast cancer cells in vivo and in vitro. It does this via modulation of NF-kβ signaling pathways (Li F, et al. Int J Clin Pharmacol Ther. 2012;50(10):712-21). These acids also inhibit the expression profile of downstream genes involved in cell proliferation (cyclin D1 and c-Myc), anti-apoptosis (Bcl-2), invasion (MMP-9), and angiogenesis (VEGF, IL-6 and IL-8)

Coriolus versicolor extract can suppress proliferation in three of four breast cancer cell lines tested, comparable to the chemotherapeutic drug, mitomycin C. Multiple cell signaling pathways are involved in this effect, including upregulation of p53 expression and downregulation of Bcl-2 expression in different cell lines (Ho CY, et al. Cancer Biol Ther. 2005:4(6):638-44).

A meta-analysis of thirteen clinical trials provided strong evidence that Coriolus (also known as Trametes versicolor) can confer survival benefits to people with breast, gastric, and colorectal carcinoma. Treatment with Coriolus gave a 9% absolute reduction in 5-year mortality with one additional patient alive for every 11 patients treated with chemotherapy (Eliza WL, et al. Recent Pat Inflamm Allergy Drug Discovery. 2012;6(1):78-87).

Phellinus linteus, known as “Black Hoof Mushroom” owing to its shape and color, contains compounds that induce apoptosis in cancer cells while strengthening immune system responsiveness. Phellinus extracts can block proliferation and colony formation of highly invasive human breast cancer cells via cell cycle arrest and up-regulation of p27 expression. It also inhibits cell adhesion, migration and invasion via suppression of uPA secretion, while also blocking angiogenesis through down-regulation of multiple signaling pathways (Silva D, et al. Br J Cancer. 2008;98(8):1348-56).



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