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.
BACKGROUND
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 the 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 PC-3 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).


METHODS
Male nude mice (n =12) were inoculated with 3x10(6) prostate cancer PC-3 cells and 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, tumors were excised, weighed and processed for histology.


RESULTS
The results showed inhibition of tumor growth in Group B. Histological studies revealed inhibition of MMP-9 and VEGF secretion and mitosis in Group B tissues.


CONCLUSIONS
Nutrient supplementation strongly suppressed the growth of tumors without any adverse effects in nude mice, suggesting strong potential as an anticancer agent.
Roomi
M Waheed
MW
Matthias Rath Research, Cancer Division, Santa Clara, CA 95050, USA.
Ivanov
Vadim
V
Kalinovsky
Tatiana
T
Niedzwiecki
Aleksandra
A
Rath
Matthias
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000494:pharmacology*; D004032:Diet; D005069:Evaluation Studies as Topic; D005353:Fibronectins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology; D008297:Male; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009077:Mucins / Q000096:biosynthesis / Q000187:drug effects; D009368:Neoplasm Transplantation; D010936:Plant Extracts / Q000494:pharmacology; D011392:Proline / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013662:Tea / Q000737:chemistry; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D045424:Complex Mixtures; D005353:Fibronectins; D019394:Ki-67 Antigen; D009077:Mucins; D010936:Plant Extracts; D013662:Tea; D042461:Vascular Endothelial Growth Factor A; D011392:Proline; D020782:Matrix Metalloproteinases; D008239:Lysine; D001205:Ascorbic Acid