Pooja Dua1, Rajiv P Gude. 1. Department of Chemotherapy, Advanced Centre for Treatment Research & Education in Cancer, Cancer Research Institute, Kharghar, 410208 Navi Mumbai, India. rpgude@yahoo.com
Abstract
PURPOSE: 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. CONCLUSION: The results suggest that PTX even at non-toxic pharmacological concentrations acts as an effective antiproliferative agent with significant antiproteolytic and antiadhesive effects.
PURPOSE:Pentoxifylline (PTX), a methylxanthine 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. CONCLUSION: The results suggest that PTX even at non-toxic pharmacological concentrations acts as an effective antiproliferative agent with significant antiproteolytic and antiadhesive effects.
Authors: Fernando S F Guimarães; Lucas F Andrade; Sharon T Martins; Ana P R Abud; Reginaldo V Sene; Carla Wanderer; Inés Tiscornia; Mariela Bollati-Fogolín; Dorly F Buchi; Edvaldo S Trindade Journal: BMC Cancer Date: 2010-03-25 Impact factor: 4.430
Authors: Miroslav Barancik; Viera Bohacova; Lenka Gibalova; Jan Sedlak; Zdena Sulova; Albert Breier Journal: Int J Mol Sci Date: 2011-12-28 Impact factor: 5.923
Authors: Darshana S Jain; Rajani B Athawale; Amrita N Bajaj; Shruti S Shrikhande; Peeyush N Goel; Yuvraj Nikam; Rajiv P Gude Journal: Daru Date: 2014-01-10 Impact factor: 3.117