In vivo and in vitro antitumor effect of ascorbic acid, lysine, proline and green tea extract on human melanoma cell line A2058.
BACKGROUND
Melanoma, a very serious form of skin cancer, causes the most skin cancer-related deaths, due to metastasis. Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling. MMPs, VEGF, Ki-67 (proliferative protein) and constituents of ECM play a critical role in angiogenesis, and are crucial in neoplastic invasion and metastasis.


METHODS
The effect of a diet (NM) containing lysine, proline, arginine, ascorbic acid and green tea extract on the growth of tumors induced by implanting human melanoma A2058 cells in athymic nude mice was examined and, also, on the expression of MMPs, VEGF and Ki-67 in these tumors. The effect of NM in vitro on the melanoma A2058 cell line was tested by measuring: cell proliferation by the MTT assay, expression of MMPs by gelatinase zymography and invasion through Matrigel.


RESULTS
Nutrient supplementation strongly suppressed the growth of tumors (by 57%)without adverse effects in nude mice. Histological studies supported these findings by showing inhibition of MMP-9 and VEGF secretion and mitotic index. In vitro, NM inhibited melanoma cell growth by 64% at 500 microg/ml and Matrigel invasion by 95% at 100 microg/ml NM.


CONCLUSIONS
These results suggest that NM may have a therapeutic potential in melanoma.
Roomi
M Waheed
MW
Dr. Rath Research Institute, Cancer Division, Santa Clara, CA 95050, USA.
Ivanov
Vadim
V
Netke
Shirang
S
Kalinovsky
Tatiana
T
Niedzwiecki
Aleksandra
A
Rath
Matthias
M
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002455:Cell Division; D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D006801:Humans; D007797:Laminin; D008239:Lysine / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000494:pharmacology*; D011392:Proline / Q000494:pharmacology*; D011509:Proteoglycans; D013662:Tea / Q000737:chemistry*; D014183:Transplantation, Heterologous
D004338:Drug Combinations; D007797:Laminin; D010936:Plant Extracts; D011509:Proteoglycans; D013662:Tea; C059485:matrigel; D003094:Collagen; D011392:Proline; D008239:Lysine; D001205:Ascorbic Acid