Antitumor effect of a combination of lysine, proline, arginine, ascorbic acid, and green tea extract on pancreatic cancer cell line MIA PaCa-2.
BACKGROUND
Current treatment of pancreatic cancer is generally associated with poor prognosis, even if diagnosed early, owing to its aggressive rate of metastasis and non-responsiveness to chemotherapy and radiotherapy. Matrix metalloproteinases (MMPs) have received much attention in recent years for their role in various malignancies, and have been implicated in tumor invasion, metastasis, and angiogenesis.


OBJECTIVE
Reported antitumor properties of ascorbic acid, lysine, proline, and green tea extract prompted us to investigate the effect of a combination of lysine, proline, arginine, ascorbic acid, and green tea extract on pancreatic cancer cell line MIA PaCa-2 for viability, MMP expression, invasion, and morphology.


METHODS
Viability was evaluated based on cell proliferation by MTT assay and MMP expression in condition media by gelatinase zymography. Invasion through Matrigel was assayed and morphology was observed by hematoxylin and eosin (H+E)staining. Data was analyzed by independent sample "t" test.


RESULTS
The nutrient mixture (NM) did not inhibit cell proliferation at 10 microg/mL and exhibited a dose-dependent antiproliferative effect with maximum inhibition of 38% over the control at 1000 microg/mL. Zymography demonstrated production of only MMP-9, which showed a dose-dependent decreased expression that was abolished at 100 microg/mL of NM. Invasion through Matrigel was inhibited at 10, 50, 100, and 500 microg/mL by 66%, 66%, 87% and 100%, respectively. H&E staining did not indicate changes even at the highest concentration of NM.


CONCLUSIONS
Our results suggest that the formulation of green tea extract, lysine, proline, and ascorbic acid, tested as a promising adjunct to standard treatment of pancreatic cancer, by inhibiting MMP expression and invasion without toxic effects important parameters in cancer metastasis.
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
D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D008239:Lysine / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011392:Proline / Q000494:pharmacology*; D013662:Tea; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D013662:Tea; D001120:Arginine; D011392:Proline; D020782:Matrix Metalloproteinases; D008239:Lysine; D001205:Ascorbic Acid