The present study therefore provides biological evident supporting the efficacy of HDN against Fe-induced toxicity in rats. [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69],

[70], [71], [72], [73], [74], [75], [76], [77] and [78]. “
“Protein kinases play an important role in the resistance of cancer cells to the cytotoxic effects of chemotherapeutic Caspase inhibitor clinical trial drugs. Mutations and aberrant activation of this class of enzymes is often linked to alteration of intracellular signal transduction pathways that control cell growth, PD-1 antibody differentiation, survival and motility [for a review see [1]]. Consequently, the connection between deregulated protein kinases and cancer led to the identification of small molecule compounds able to regulate the activity of this class of enzymes. In this respect, previous research focusing on the selection of compounds with a unique specificity towards individual protein kinases has shifted, in recent years, to the identification of drugs with broad specificity but high toxicity, thus, representing a therapeutic alternative to current treatment regimens. Protein kinase CK2 is a pleiotropic and constitutively active serine/threonine

kinase composed of two catalytic subunits α and/or α’ and two regulatory β-subunits. Evidence so far collected, suggests that this enzyme plays a significant role in regulating cell survival and conferring resistance to apoptotic cell death [2], [3] and [4]. In this respect, studies on pancreatic cancer cells, that are notoriously resistant to chemotherapeutic

drugs currently employed in the clinics, revealed that down-regulation of CK2 by RNA interference significantly enhances cell death induced by gemcitabine (2’,2’-difluoro 2’-deoxycytidine) treatment [5]. Perhaps, this effect should not come as a surprise since overexpression of CK2 has been documented in all cancer types so far investigated Branched chain aminotransferase and associated with the aggressiveness of the tumour [2] and [6]. Higher than average CK2 activity offers a number of selective advantages to the tumours, hence, its inhibition or down-regulation would consequently weaken this growth advantage. In this respect, the identification of small molecule compounds able to inhibit significantly the activity of CK2 has become an important goal for the successful treatment of cancer. Recently, the screening of small molecule compound libraries provided by the National Cancer Institute (NCI) under the Developmental Therapeutics Program (DTP), has led to the identification of C11 a two-components (i.e. PCP and DMA) cell permeable mixture able to inhibit endogenous CK2 and induce significant cell death in human pancreatic cancer cells.