Unravelling the antimetastatic potential of pentoxifylline, a methylxanthine derivative in human MDA-MB-231 breast cancer cells
- 338 Downloads
Pentoxifylline (PTX), a methylxanthine derivative is a non-steroidal immunomodulating agent with unique hemorheologic properties. It is used in the treatment of intermittent claudication as it increases the amount of oxygen reaching tissues by increasing the flexibility of red blood cells. Recently, it has also shown to exhibit anti-metastatic and anti-angiogenic activities in B16F10 melanoma cells both in vitro as well as in vivo. As per the reports, the choice of drug in the treatment of breast cancer is paclitaxel, but the major limitation is its toxicity. However, the effects of PTX on metastatic processes in breast cancer are not currently known. Therefore, in this study, we have examined the effect of PTX in MDA-MB-231 human breast cancer cells. The MTT assay showed dose- and time-dependent decreases in cellular proliferation. The non-toxic concentration of PTX selected were 1, 2.5 and 5 mM for 24 h. PTX induced a G0-G1 cell-cycle arrest leading to apoptosis. Further, it affected adhesion to both the matrigel and collagen type-IV in a time- and dose-dependent manner. The PTX impeded the migration of MDA-MB-231 cells and also decreased the activities of both MMP-2 and MMP-9. Thus, PTX at non-toxic doses affected cellular proliferation, adhesion, migration and invasion. These results demonstrate its anti-metastatic effect on MDA-MB-231 cells, and further studies need to be carried out to understand the mechanism of action.
KeywordsPentoxifylline MDA-MB-231 breast cancer cells Proliferation Adhesion Migration Matrix-metalloproteinases
The authors acknowledge the support of grant from the ACTREC, Tata Memorial Centre. Mr. Peeyush N. Goel is supported by CSIR-Junior Research Fellowship. The authors would also like to thank Shimul Salot for providing technical assistance.
Conflict of Interest
- 30.Chen TC, Wadsten P, Su S, Rawlinson N, Hofman FM, Hill CK, Schonthal AH (2002) The type IV phosphodiesterase inhibitor rolipram induces expression of the cell cycle inhibitors p21(Cip1) and p27(Kip1), resulting in growth inhibition, increased differentiation, and subsequent apoptosis of malignant A-172 glioma cells. Cancer Biol Ther 1:268–276PubMedGoogle Scholar
- 40.Okada Y, Tsuchiya H, Shimizu H, Tomita K, Nakanishi I, Sato H, Seiki M, Yamashita K, Hayakawa T (1990) Induction and stimulation of 92-kDa gelatinase/type IV collagenase production in osteosarcoma and fibrosarcoma cell lines by tumor necrosis factor alpha. Biochem Biophys Res Commun 171:610–617PubMedCrossRefGoogle Scholar