In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human colon cancer cell HCT 116 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry.
Colorectal cancer is the second most deadly cancer in the United States. When diagnosed early, current treatments bring a limited success; however, once metastasis occurs, radiation and chemotherapy are generally ineffective. Structural changes in the ECM are necessary for cell migration during tissue remodeling. Matrix metalloproteinases (MMPs), VEGF, Ki-67 (proliferative protein), and constituents of ECM, such as fibronectin, play a critical role in angiogenesis and are thus 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 (NM) on the growth of tumors, induced by implanting human colon HCT 116 cancer cells in athymic nude mice, and 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 to 6 week-old athymic male nude mice (n=12) were inoculated with 3x10(6) colon cancer HCT 116 cells. After injection, the mice were randomly divided into 2 groups; group A was fed a regular diet and group B was fed a regular diet supplemented with 0.5% NM. The mice were sacrificed 4 weeks later, and their tumors were excised, weighed, and processed for histology. Results showed that the nutrient mixture (NM) inhibited growth and reduced the size of tumors in nude mice. Furthermore, histological evaluation revealed increased mitotic index, MMP-9 and VEGF secretion and reduced basement membrane 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, which are critical parameters for cancer control and prevention.
Roomi
M Waheed
MW
MRI, Cancer Research Division, 1260 Memorex Drive, 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*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000662:veterinary; D004032:Diet; D018450:Disease Progression; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008239:Lysine / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009077:Mucins / Q000096:biosynthesis; D009374:Neoplasms, Experimental; D011392:Proline / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000975:Antioxidants; D019394:Ki-67 Antigen; D009077:Mucins; D013662:Tea; D042461:Vascular Endothelial Growth Factor A; D011392:Proline; D020782:Matrix Metalloproteinases; D008239:Lysine; D001205:Ascorbic Acid