Antiproliferative and antiproteolytic activity of pentoxifylline in cultures of B16F10 melanoma cells.
OBJECTIVE
Pentoxifylline (PTX), a methyl xanthine derivative is widely used as a haemorheological agent in the treatment of peripheral vascular disease. In the present study, we investigated the in vitro effects of PTX on B16F10 melanoma cell proliferation, adhesion and secretion of Matrix metalloproteinases.


METHODS
The toxic range of PTX was evaluated using MTT test and colony formation assay. The cell cycle study of PTX treated cells was carried out using flow cytometric analysis. Adhesion assay of pretreated melanoma cells was carried out on extracellular matrix (ECM) substrates. The relative levels and activity of matrix metalloprotienase-9 (MMP-9) and MMP-2 were determined by gelatin zymography and western blotting.


RESULTS
Pentoxifylline significantly inhibited the in vitro proliferation of B16F10 cells in a concentration dependent manner and displayed an IC(50) of 15.2 mM. Non-cytotoxic concentration of 1-3 mM of PTX for an exposure of 24 h demonstrated significant changes in cell morphology. A significant inhibition in G1-S phase transition was observed on PTX treatment. Pretreated F10 cells showed inhibition in adhesion to ECM components and markedly inhibited the secretion of MMP-9 and MMP-2 gelatinases.


CONCLUSIONS
The results suggest that PTX even at non-toxic pharmacological concentrations acts as an effective antiproliferative agent with significant antiproteolytic and antiadhesive effects.
Dua
Pooja
P
Department of Chemotherapy, Advanced Centre for Treatment Research & Education in Cancer, Cancer Research Institute, Kharghar, 410208 Navi Mumbai, India. rpgude@yahoo.com
Gude
Rajiv P
RP
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006868:Hydrolysis; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology*
D009363:Neoplasm Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010431:Pentoxifylline