1 research outputs found
Toxicology and Applied Pharmacolog
Carbonic anhydrase inhibitors have emerged in the past few years as an
interesting candidate for the development of novel unconventional strategies. Despite
their effect in tumor regression via inhibition of tumor acidification, their potential role is
not yet fully elucidated. Herein, we investigated whether Acetazolamide (AZ) could
modulate Imatinib (IM) anticancer activity, both in breast cancer cells (T47D) and in
isolated tumor specimens of Ehrlich ascites carcinoma (EAC). The impact of this
combination on angiogenesis was evidenced by decreasing PDGF-A expression and
enhancing that of TSP-1. In the meantime, AZ significantly suppressed IM-induced
attenuation of VEGF secretion in T47D cells, most probably due to NO inhibition. The
combination also dramatically decreased the metastatic activity of T47D cells by
mitigating the protein levels of MMP-2, -9 and phosphorylation of p38 MAPK, while
increasing the expression of TIMP-1 and -2. In addition, a strong proapoptotic effect was
observed in T47D cells after combining AZ and IM in terms of increased caspase-9 and -
3 activities. Interestingly, these results were confirmed by the reduction in the isolated
tumor volume, MVD, Ki-67 and VEGF expression. Eventually, the study provides a new
therapeutic strategy for treating cancer