title: Antineoplastic activity of a nutrient mixture in Y-79 malignant retinoblastoma             cells.
abstract: Retinoblastoma is one of the most common ocular malignancies in children             under the age of six. Occasionally, retinoblastoma metastasizes to extraocular             organs including the bone, lung and brain. Left untreated, retinoblastoma is fatal.             At present, there is no effective treatment for metastatic retinoblastoma. We             investigated the antineoplastic activity of a nutrient mixture (NM) (lysine, proline,             ascorbic acid and green tea extract) at concentrations of 10, 50, 100, 500 and             1,000 µg/ml in triplicate at each dose in the human malignant retinoblastoma Y-79             cell line. The parameters used were cell proliferation, expression of matrix metalloproteinases             (MMPs), invasion through Matrigel, morphology and apoptosis. Cell viability was             assessed by trypan blue dye exclusion test. Invasion was evaluated through Matrigel             and MMP activity by gelatinase zymography. H&E staining for morphological             cell alterations and apoptotic studies using the Live Green Poly Caspase Detection             kit were also conducted. The nutrient mixture at 10-100 µg/ml demonstrated approximately 25%             toxicity towards Y-79 retinoblastoma cells and significant toxicity at 500 and 1,000 µg/ml.             The Y-79 cells secreted only MMP-2 as demonstrated by zymography; the nutrient             mixture had no effect on MMP-2 expression up to 100 µg/ml, but completely blocked             it at 500 µg/ml. Importantly, Y-79 retinoblastoma cells were not invasive through             Matrigel. H&E staining showed cell morphological changes related to apoptosis,             which was confirmed using the Live Green Poly Caspase Detection kit. Our results             suggest that this nutrient mixture, which inhibited cell proliferation, expression             of MMP-2 and induced apoptosis, may be a candidate for further exploration for             its therapeutic potential in metastatic retinoblastoma.
authors.affiliation: Dr Rath Research Institute, Cancer Division, Santa Clara, CA 95050, USA.
authors.forename: M Waheed
authors.initials: MW
authors.lastname: Roomi
authors.forename: Nusrath
authors.initials: N
authors.lastname: Roomi
authors.forename: Bilwa
authors.initials: B
authors.lastname: Bhanap
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Niedzwiecki
authors.forename: Matthias
authors.initials: M
authors.lastname: Rath
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008239:Lysine / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D011392:Proline / Q000737:chemistry; D012175:Retinoblastoma / Q000473:pathology* / Q000517:prevention & control*; D013662:Tea; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D010936:Plant Extracts; D013662:Tea; D011392:Proline; D008239:Lysine; D001205:Ascorbic Acid