Anticancer Activity of a Nutrient Mixture in Malignant Leukemia Cell Line P-388 in vitro #96

M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath Matthias Rath Research Institute, Cancer Division, Santa Clara, CA 95050 Presented at: International Society for Biological Therapy of Cancer, Nov 10-13, 2005, Alexandria, VA Published in: International Society for Biological Therapy of Cancer Proceedings, Abstract #96

Abstract Introduction: A unique nutrient formulation (NM) consisting of lysine, proline, ascorbic acid and green tea extract has been shown to exhibit anti-tumor effects in several cancer lines both in vitro and in vivo studies. NM acts by exerting a potent synergistic anticarcinogenic effect by inhibiting proliferation, MMP expression, and invasion through Matrigel. Leukemia, acute or chronic neoplasia, is a disorder of bone marrow in which unrestrained proliferation of white blood cells occurs, resulting in formation of metastatic colonies and penetration through matrix barriers and blood vessel walls, a process mediated through MMPs. Objective: In the present investigation we examined the anticancer effect of NM on murine leukemia cell line P-388 on proliferation, MMP expression and invasion through Matrigel Materials and Methods: Murine leukemia cell line P-388D1 (ATCC) was grown in DEM media in 10% horse serum and antibiotics, and treated with NM at 0, 10, 50, 100, 500, and 1000 g/ml concentration in triplicate at each dose. Cell proliferation was assessed by MTT assay, invasion through Matrigel, and MMPs by gelatinase zymography. Cells were also treated with PMA (200 ng/ml) for MMP-9 induction. Results: NM exhibited slight toxicity at 50 g/ml and significant (70% and 90% over the control) antiproliferative effect at 500 and 1000 g/ml respectively,. Invasion through Matrigel was inhibited at 500 and 1000 g/ml by 80% and 100% respectively. However, no MMP (-2 or 9) activity was detected even with PMA treatment of P-388 cells. Conclusion: Our results suggest that NM is a promising new therapeutic agent for leukemia,

and is a potential candidate for human trials.

Comment: Leukemia, a disorder of bone marrow characterized by unrestrained white blood cell proliferation, results in formation of metastatic colonies and penetration through matrix barriers and blood vessel walls. Degradation and invasion through matrix barriers and vessel walls is mediated by secretion of MMPs. A nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract exhibited significant inhibition of Matrigel invasion (with total block at 1000 g/ml) and significant antiproliferative effect at 500 g/ml (70%) and 1000 g/ml (90%). These results are important as they indicate NM is a promising therapeutic agent for leukemia.

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