M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division, Santa Clara, CA 95050
47th Annual Meeting of the American College of Nutrition, October 5-8, 2006, Reno, NV
Journal of the American College of Nutrition vol 25(5), October 2006, abstract #23
Hemangiomas, the most frequent vascular tumors in Caucasian infants, occur in approximately 1% of normal newborns, but the incidence increases to 20% in premature infants weighing less than 1000 gm. These lesions are characterized by rapid proliferation of capillaries during the first year of life, followed by a slowed growth and regression of the tumor over the next 5-6 years, with complete regression of the lesion by the age of 6-12 years. Approximately 5% of hemangiomas cause serious tissue damage, while 1-2% are life threatening. However, the pathogenesis of these tumors is still largely unknown and the current therapy, such as systemic corticosteroid, vincristine, and interferon-alpha, is toxic and remains unsatisfactory. A nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract has shown significant anti-angiogenic and anti-tumor effect against a number of cancer cell lines.
Using a mouse hemangioendothelioma model, we investigated the efficacy of NM. We also tested the effect of NM in vitro, evaluating viability, MMP secretion, invasion and morphology.
Athymic nude mice, 5-6 weeks old, were inoculated with 3x106 EOMA cells (ATCC) subcutaneously and randomly divided into two groups; group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. 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, measuring cell proliferation by MTT assay, invasion through Matrigel, morphology by H&E staining, and secretion of MMPs by gelatinase zymography at 0, 10, 50, 100, 500 and 1000 µg/ml concentration, in triplicate at each dose.
NM inhibited the growth of tumors by 50%. In vitro, NM exhibited dose response toxicity with 10%, 30% and 55% at 10, 100 and 1000 µg/ml. Invasion through Matrigel was inhibited at 10, 50, 100 and 500 µg/ml by 20%, 25%, 30% and 100% respectively. H&E did not indicate any changes even at highest concentration. Interestingly EOMA cell did not demonstrate any MMP activity by zymography.
These results suggest that NM may have therapeutic potential in treating infantile hemangioendotheliomas and, perhaps, other cutaneous vascular tumors.
Current treatment for infantile hemangioendothelioma includes toxic agents such as systemic corticosteroids, vincristine, and interferon-alpha. We investigated the effect of a unique non-toxic micronutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract, which has shown significant anti-angiogenic and anti-tumor effect against a number of cancer cell lines, on nude mice injected subcutaneously with EOMA cells. In addition, we tested NM in vitro on EOMA cells evaluating its effect on cell proliferation, invasion, and cell morphology. NM inhibited the growth of tumors by 50% and exhibited dose response toxicity and inhibition of EOMA Matrigel invasion. EOMA cell morphology was not affected even at highest concentration tested. These results are significant as they indicate NM is a potential non-toxic alternative agent for treatment of infantile hemangioendothelioma.