Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited...
The tumor suppressor p53 is a transcription factor that regulates key processes. But, the outcomes of the p53 response go beyond its role as a nuclear transcription factor. Sirtuin (SIRT1) regulates p53 functions as transcription factor. At the same time, SIRT1 protects the genome under stress conditions. The link between p53 and SIRT1 responses is...
Cancer cells depend on an altered energy metabolism characterized by increased rates of both glycolysis and glutaminolysis. Accordingly, corresponding key metabolic enzymes are overexpressed or hyperactivated. As a result, this newly acquired metabolic profile determines most other cancer hallmarks including resistance to cell death. Recent finding...
Valproic acid (VPA) exhibits important pharmacological properties but has been reported to trigger side effects, notably on the hematological system. We previously reported that VPA affects hematopoietic homeostasis by inhibiting erythroid differentiation and promoting myeloid and megakaryocyte differentiation. Here, we analyzed the effect of VPA o...
Carcinogenesis is a complex and multistep process that involves the accumulation of successive transformational events driven by genetic mutations and epigenetic alterations that affect major cellular processes and pathways such as proliferation, differentiation, invasion and survival. Massive deregulation of all components of the epigenetic machin...
•act as activators of specific apoptotic commitments•modulate the stress balance and equilibrate between death and survival•target prosurvival and pro-death pathways•inhibit NF-kB-regulated survival genes
The use of energy restriction mimetic agents (ERMAs) to selectively target cancer cells addicted to glycolysis could be a promising therapeutic approach. Thiazolidinediones (TZDs) are synthetic agonists of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ that were developed to treat type II diabetes. These compounds also disp...
Valproic acid (VPA) exhibits important pharmacological properties but has been reported to trigger side effects, notably on the hematological system. We previously reported that VPA affects hematopoietic homeostasis by inhibiting erythroid differentiation and promoting myeloid and megakaryocyte differentiation. Here, we analyzed the effect of VPA o...
Here we describe the synthesis and biological activity of novel amino-pyrazolopyridines with anti-NF-κB and pro-apoptotic potential. α-Methylene ketones were used as a starting point for synthesis of amino-pyrazolopyridine 3. The alkylidene malononitriles 1 were obtained by the Knoevenagel reaction of ketones with malononitriles. Vilsmeier-Haack re...