Gene expression profiles involved in survival and progression pathways modulated by oligoelements and lachesis muta venom in MDA-MB-231 breast cancer cells using expression macroarray analysis

E. J. CRESCENTI; V. MEDINA; M. CROCI; R. BERGOC; F. SANCHEZ-JIMENEZ; E. S. RIVERA.

May 20-, 2008, Atlanta, Georgia, USA.

Congreso; 44th Annual Meeting of the American Society of Clinical Oncology ASCO. May 20-, 2008, Atlanta, Georgia, USA.; 2008

American Society of Clinical Oncology

We have previously reported that the combination of oligoelements (Se, Zn, Mn) plus Lachesis muta venom (O-LM) significantly inhibits proliferation of malignant human cell lines including breast cancer cells like MCF-7 and MDA-MB-231. The effect of O-LM was associated with an induction of cell cycle arrest, differentiation and apoptosis. Furthermore, O-LM increased survival of animals with experimental tumors by additionally producing an up-regulation of innate and T-cell mediated immunity (ASCO Proceedings 2006, 2007). In the present work we analyzed the gene expression profiles using PCR array analysis and identified several genes in the angiogenic and survival pathways that are modulated by O-LM in MDA-MB-231 cells.Methods: The amount of cDNA was determined using cDNA GEarray (SuperArray Biosciences). After subtracting the background, the signal intensity of each single spot was normalized to that of the ribosomal protein L13a. Similar results were obtained with other housekeeping genes (b-actin, GAPDH). Results were expressed as the mean ± SEM of the expression ratios of O-LM-treated vs. untreated cells from triplicatesResults:O-LM markedly up-regulated expression of genes related to growth inhibition and apoptosis as INFa,g; IL-8, TNFa (5, 6, 3, 6.3-fold, respectively). Conversely, O-LM increased expression of genes linked to migration and angiogenesis like EDG1; EFNA2; ETS-1; FGF1,6; FGFR1, VEGFB; GRO1; ITGB3; MMP2, MMP9, HIF1A, MDK, (5, 5.3, 5.8, 4, 6, 3.2, 1.5, 2.1, 6, 5.9, 4.7, 3.2, 4.5-fold) while decreased the expression of TGFB1;TGFR2;TIMP-1.By using different techniques like RT-PCR, Western blot, among others we further confirmed the effect of O-LM on gene expression profile of the breast cancer cells. Conclusions:The therapeutic action of O-LM is based on its ability of targeting simultaneously multiple pathways involved in cancer development and progression. Present study clearly demonstrates the capacity of O-LM to modulate the expression of different genes related to angiogenic and survival pathways that are correlated with the mediated signaling processes previously reported