BreastDefend™ prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer

• Published in: Oncology reports Vol. 28; no. 4; pp. 1139 - 1145
• Main Authors: JIANG, JIAHUA, THYAGARAJAN-SAHU, ANITA, LOGANATHAN, JAGADISH, ELIAZ, ISAAC, TERRY, COLIN, SANDUSKY, GEORGE E, SLIVA, DANIEL
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.10.2012; Spandidos Publications UK Ltd
• Subjects: Administration, Oral; Animals; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Agents, Phytogenic - pharmacology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; C-X-C chemokine receptor-4; Cancer therapies; Cell Line, Tumor; dietary supplement; Dietary supplements; Dietary Supplements - adverse effects; Disease Models, Animal; Down-Regulation; Female; Gene Expression Regulation, Neoplastic - drug effects; Good Manufacturing Practice; Humans; Laboratory animals; Lung cancer; lung cancer metastasis; Lung Neoplasms - genetics; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Metastasis; Mice; Mice, Nude; Plant Extracts - adverse effects; Plant Extracts - pharmacology; Plants, Medicinal - chemistry; Proteins; Receptors, CXCR4 - genetics; Toxicity; Toxicity Tests; triple negative breast cancer cells; Tumors; urokinase plasminogen activator; Urokinase-Type Plasminogen Activator - genetics; Xenograft Model Antitumor Assays; United States > US
• DOI: 10.3892/or.2012.1936
• ISSN: 1021-335X

We have recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of MDA-MB-231 invasive human breast cancer cells in vitro. In the present study, we evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. Oral application of BD (100 mg/kg of body weight for 4 weeks) by intragastric gavage did not affect body weight or activity of liver enzymes and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. Moreover, BD significantly decreased the change in tumor volume over time compared to the control group (p=0.002). BD treatment also markedly decreased the incidence of breast-to-lung cancer metastasis from 67% (control) to 20% (BD) (p<0.05) and the number of metastases from 2.8 (0.0, 48.0) in the control group to 0.0 (0.0, 14.2) in the BD treatment group (p<0.05). Finally, anti-metastatic activity of BD in vivo was further confirmed by the downregulation of expression of PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4) genes in breast tumors. In conclusion, BD may be considered as a biological therapeutic agent against invasive breast cancers.