In Vivo Antitumor Effect of Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Prostate Cancer PC-3 Xenografts in Nude Mice: Evaluation of Tumor Growth and Immunohistochemistry

M.W. Roomi, V.Ivanov, T.Kalinovsky, A. Niedzwiecki, M.Rath
In Vivo 2005, 19(1): 179-184.

Prostate cancer, a highly metastatic cancer, is the second most deadly cancer in the United States. Cancer cell invasion through the extracellular matrix (ECM), and subsequent metastasis is dependent upon degradation of the ECM. Matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), Ki 67 (proliferative protein), and constituents of ECM play a critical role in angiogenesis, and are crucial in neoplastic invasion and metastasis.

Based on antitumor properties of certain nutrients, we investigated the effect of a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract on the growth of tumors induced by implanting human prostate cancer PC3 cells in athymic nude mice and on the expression of MMPs, VEGF, Ki 67 and fibronectin in these tumors, as well as the production of mucin (by PAS staining). After one-week of isolation, 5-6 week old athymic male nude mice (n=12) were inoculated with 3x106 prostate cancer PC-3 cells. After injection, the mice were randomly divided into two groups; group A was fed a regular diet and group B was fed a regular diet supplemented with 0.5% of the nutrient mixture (NM). Four weeks later, the mice were sacrificed, and their tumors were excised, weighed, and processed for histology. Results showed that the nutrient mixture NM-supplemented diet inhibited the growth of tumors in nude mice. Furthermore, histological evaluation revealed increased mitotic index and MMP-9 and VEGF secretion in the control group tissues. Nutrient supplementation strongly suppressed the growth of tumors without any adverse effects in nude mice, suggesting the nutrient combination has potential as an anticancer agent. Histological studies supported these findings by showing inhibition of MMP-9 and VEGF secretion and mitotic index - critical parameters for cancer control and prevention.

Key Words:
Prostate cancer, nude mice, xenograft, ki 67, MMP, green tea extract, ascorbic acid, lysine, proline

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