Lipoprotein(A) And Vitamin C Impair Development Of Breast Cancer Tumors In Lp(A)+; Gulo-/- Mice

John Cha*, M. Waheed Roomi*, Tatiana Kalinovsky, Aleksandra Niedzwiecki, Matthias Rath

*Contributed equally

Dr. Rath Research Institute, Santa Clara, California, USA
International Journal of Oncology    DOI: 10.3892/ijo.2016.3597 

 

Abstract:
Cancer progression is characterized by loss of extracellular matrix (ECM) integrity, which is a precondition for tumor growth and metastasis. In order to elucidate the precise mechanisms of ECM degradation in cancer we used a genetically modified mouse mimicking two distinct human metabolic features associated with cancerogenesis - the lack of endogenous vitamin C synthesis and the production of human Lp(a).  Female Lp(a)+;Gulo(-/-) and control wild type Balb/c mice without these two metabolic features were orthotopically inoculated with 4T1 breast cancer cells (5x105).

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In vivo and in vitro effects of a nutrient mixture on breast 4T1 cancer progression

M.W. Roomi, T. Kalinovsky, N.M. Roomi, J. Cha, M. Rath, A. Niedzwiecki
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
International Journal of Oncology 2014, DOI: 10.3892/ijo.2014.2379

Abstract: 
Long-term survival of patients with breast cancer remains poor, due to metastasis and recurrence. We investigated the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract in vivo and in vitro on murine 4T1 breast cancer, a representative model for metastatic breast cancer. After one week of isolation, 5-6 week old female Balb/C mice were inoculated with 5x105 4T1 cells into the mammary pad and randomly divided into two groups; the Control group was fed a regular diet and the NM group a regular diet supplemented with 0.5% NM. After four weeks, the mice were sacrificed and their tumors, lungs, livers, kidneys, hearts and spleens were excised and processed for histology.

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Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C deficient mice

J. Cha, M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
International Journal of Oncology 2013,  42: 55-64

Abstract
Degradation of the extracellular matrix (ECM) plays a critical role in the formation of tumors and metastasis and has been found to correlate with the aggressiveness of tumor growth and invasiveness of the cancer. Ascorbic acid, which is known to be essential for the structural integrity of the intercellular matrix, is not produced by humans and must be obtained from the diet. Cancer patients have been shown to have very low reserves of ascorbic acid.

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Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human female cancer cell lines

M.W. Roomi, T. Kalinovsky, M. Rath and A. Niedzwiecki
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Oncology Reports 2012, DOI:10:3892/or.2012.1879

Abstract:
Cancers of the breast, cervix, uterus and ovary are the most prevalent cancers in women worldwide. Proteases play a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. Strong clinical and experimental evidence demonstrates association of elevated levels of urokinase plasminogen activators (u-PA) and matrix metalloproteinases (MMPs) with cancer progression, metastasis and shortened patient survival. MMP activities are regulated by specific tissue inhibitors of metalloproteinases (TIMPS).

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In Vitro and In Vivo Antitumorigenic Activity of a Mixture of Lysine, Proline, Ascorbic Acid and Green Tea Extract on Human Breast Cancer Lines MDA-MB-231 and MCF-7

M.W. Roomi, V.Ivanov, T.Kalinovsky, A. Niedzwiecki, M.Rath
Medical Oncology 2005, 22(2): 129-38

Abstract:
Current treatments are generally ineffective once breast cancer has metastasized; median survival is reduced to 2-3 years. Previous research studies demonstrating potent synergistic antitumor activity of lysine, proline, ascorbic acid and epigallocatechin gallate prompted us to investigate the in vivo inhibitory effect of a nutrient mixture containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate (NM) on the growth of human cancer xenografts in female athymic nude mice. 5-6 week old female mice were inoculated with 3x106 breast cancer cells MDA-MB-231. After injection, the mice were randomly divided into two groups A and B; group A was fed a regular diet and group B with the regular diet supplemented with 0.5% of the nutrient mixture. Four weeks later, the mice were sacrificed, and their tumors were excised, weighed, and processed for histology. We also tested the effect of NM in vitro on estrogen-receptor positive (ER+) MCF-7 and estrogen-receptor negative (ER-) MDA-MB-231 breast cancer cell lines by measuring: cell proliferation by MTT assay, expression of MMPs by gelatinase zymography, invasion through Matrigel, and VEGF by ELISA. MCF-7 cells were also treated with estradiol to study enhanced invasion and expression of MMPs and VEGF.

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