Current Pharmaceutical Design - Volume 18, Issue 10, 2012

Decades of research on the mechanisms and processes leading to the development of cancer have provided a plethora of genes, proteins and physiological steps that may contribute to the generation and metastasis of the disease. However, despite many efforts, the success in chemotherapeutic intervention have not followed suit [1]. The causes of this are probably manifold and, among them, the difficulty to ta Read More

High rate of glycolysis is a metabolic hallmark of cancer. While anaerobic glycolysis promotes energy production under hypoxia, aerobic glycolysis, the Warburg effect, offers a proliferative advantage through redirecting carbohydrate fluxes from energy production to biosynthetic pathways. To fulfill tumor cell needs, the glycolytic switch is associated with elevated glucose uptake and lactic acid release. Altered glucose metabolis Read More

The acid-base balance of cells is related to the concentration of free H+ ions. These are highly reactive, and their intracellular concentration must be regulated to avoid detrimental effects to the cell. H+ ion dynamics are influenced by binding to chelator substances (‘buffering’), and by the production, diffusion and membrane-transport of free H+ ions or of the H+-bound chelators. Intracellular pH (pHi) regulation aims to bal Read More

Transformed cells suffer several changes leading to the increase of protective mechanisms and show a metabolic profile in accordance with higher proliferative capacity. In these mechanisms, changes in mitochondrial activity cause a higher glycolytic metabolism in detriment of oxidative phosphorylation. In these changes, H+-ATPase regulation seems to be importantly involved. During the last years, polyphenols and speci Read More

The Na+/H+-exchanger 1, NHE1 (SLC9A1) and the electroneutral Na+,HCO3 --cotransporter NBCn1 (SLC4A7) are coexpressed in a wide range of tissues. Under normal physiological conditions these transporters play an ostensibly similar role, namely that of net acid extrusion after cellular acidification. In addition, they have been implicated in multiple other cellular processes, including regulation of transepithelial transport, Read More

Among the many factors involved in the maintenance of homeostatic growth is the tight regulation of cellular pH. Intracellular pH of normal cells is maintained within a physiological range thanks to the activity of a number of pH regulators that respond to the acidbase shifts associated with normal cellular metabolic processes. Interestingly, there is a preponderance of evidence that dysregulation of intracellular pH is associa Read More

Cancer cells show a metabolic shift that makes them overproduce protons; this has the potential to disturb the cellular acidbase homeostasis. However, these cells show cytoplasmic alkalinisation, increased acid extrusion and endosome-dependent drug resistance. Vacuolar type ATPases (V-ATPases), together with other transporters, are responsible to a great extent for these symptoms. These multi-subunit proton pumps Read More

It is becoming increasingly acknowledged that tumorigenesis is not simply characterized by the accumulation of rapidly proliferating, genetically mutated cells. Microenvironmental biophysical factors like hypoxia and acidity dramatically condition cancer cells and act as selective forces for malignant cells, adapting through metabolic reprogramming towards aerobic glycolysis. Avoiding intracellular accumulation of lactic aci Read More

Two of the key proteins involved in tumor acidification are the V-ATPase and the tumor-associated carbonic anhydrases (CAs), such as CA IX and XII. Although there are many chemical classes of V-ATPase inhibitors, most of them are toxic for mammals and their potential use as antitumor drugs is limited. The proton pump inhibitors (PPIs), a class of antiulcer agents in clinical use for more than 30 years, have been proven to be usef Read More

During the past 20 years, we have found that acridine orange (AO) selectively accumulates in musculoskeletal sarcomas in vivo or exerts selective cytocidal effects against sarcoma cells in vitro after illumination of the tumor cells with visible light or irradiation of the cells with low-dose X-rays. Based on the data obtained from basic research, we have employed reduction surgery followed by photo- or radiodynamic therapy usin Read More

Wound healing and anti-inflammatory effects of aerial parts and roots of S. acuminata, S. cana var. alpina, S. cana var. jacquiniana, S. cana var. radicosa, S. eriophora, S. laciniata ssp. laciniata, S. suberosa ssp. suberosa and S. sublanata were investigated in current study to clarify the traditional usage of Scorzonera species growing in Turkey. It is well known that some species of the Scorzonera genus are used for woun Read More

Non-systemic drugs act within the intestinal lumen without reaching the systemic circulation. The first generation included polymeric resins that sequester phosphate ions, potassium ions, or bile acids for the treatment of electrolyte imbalances or hypercholesteremia. The field has evolved towards non-absorbable small molecules or peptides targeting luminal enzymes or transporters for the treatment of mineral metabolis Read More