Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture             in human female cancer cell lines.
Cancers of the breast, cervix, uterus and ovary are the most prevalent cancers             in women worldwide. Proteases play a key role in tumor cell invasion and metastasis             by digesting the basement membrane and ECM components. Strong clinical and experimental             evidence demonstrates association of elevated levels of urokinase plasminogen             activators (u-PA) and matrix metalloproteinases (MMPs) with cancer progression,             metastasis and shortened patient survival. MMP activities are regulated by specific             tissue inhibitors of metalloproteinases (TIMPs). Our main objective was to study             the effect of a nutrient mixture (NM) on the activity of u-PA, MMPs and TIMPs             in human breast, cervix, uterine and ovarian cancer cell lines. Human breast (MDA-MB-231             and MCF-7), cervical (HeLa), uterine (SK-UT-1) and ovarian (SKOV3) cancer cell             lines were cultured in their respective media and treated at confluence with NM             at 0, 50, 100, 250, 500 and 1000 µg/ml. Analysis of u-PA activity was carried             out by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse zymography.             Both breast and uterine cancer cell lines expressed u-PA, which was inhibited             by NM in a dose-dependent manner. However, no bands corresponding to u-PA were             detected for HeLa and SK-OV-3 cell lines. On gelatinase zymography, MDA-MB-231             and MCF-7 showed one band corresponding to MMP-9, HeLa showed two bands, an intense             band corresponding to MMP-2 and a faint band corresponding to MMP-9, SK-UT-1 showed             PMA-induced MMP-9, and SK-OV-3 showed a band corresponding to MMP-2. NM inhibited             their expression in all cell lines. The activity of TIMPs was upregulated in all             cancer cell lines in a dose-dependent manner. Analysis revealed a positive correlation             between u-PA and MMPs and a negative correlation between u-PA/MMPs and TIMPs.             These findings suggest the therapeutic potential of NM in the treatment of female             cancers.
Department of Oncology, Dr. Rath Research Institute, Santa Clara, CA 95050, USA.
M Waheed
MW
Roomi
Tatiana
T
Kalinovsky
Matthias
M
Rath
Aleksandra
A
Niedzwiecki
D045744:Cell Line, Tumor; D003470:Culture Media / Q000737:chemistry*; D005260:Female; D018093:Gelatinases / Q000737:chemistry; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*
D003470:Culture Media; D061965:Matrix Metalloproteinase Inhibitors; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; D018093:Gelatinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9