Cancer-Linked Targets Modulated by Curcumin.
Cancer-linked targets modulated by curcumin.
Filed under: Drug and Alcohol Rehabilitation
Int J Biochem Mol Biol. 2012; 3(4): 328-51
Hasima N, Aggarwal BB
In spite of major advances in oncology, the World Health Organization predicts that cancer incidence will double within the next two decades. Although it is well understood that cancer is a hyperproliferative disorder mediated through dysregulation of multiple cell signaling pathways, most cancer drug development remains focused on modulation of specific targets, mostly one at a time, with agents referred to as “targeted therapies,” “smart drugs,” or “magic bullets.” How many cancer targets there are is not known, and how many targets must be attacked to control cancer growth is not well understood. Although more than 90% of cancer-linked deaths are due to metastasis of the tumor to vital organs, most drug targeting is focused on killing the primary tumor. Besides lacking specificity, the targeted drugs induce toxicity and side effects that sometimes are greater problems than the disease itself. Furthermore, the cost of some of these drugs is so high that most people cannot afford them. The present report describes the potential anticancer properties of curcumin, a component of the Indian spice turmeric (Curcuma longa), known for its safety and low cost. Curcumin can selectively modulate multiple cell signaling pathways linked to inflammation and to survival, growth, invasion, angiogenesis, and metastasis of cancer cells. More clinical trials of curcumin are needed to prove its usefulness in the cancer setting.
HubMed – drug
Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity.
Filed under: Drug and Alcohol Rehabilitation
Sci Rep. 2013; 3: 1035
Realini N, Solorzano C, Pagliuca C, Pizzirani D, Armirotti A, Luciani R, Costi MP, Bandiera T, Piomelli D
The expression of acid ceramidase (AC) – a cysteine amidase that hydrolyses the proapoptotic lipid ceramide – is abnormally high in several human tumors, which is suggestive of a role in chemoresistance. Available AC inhibitors lack, however, the potency and drug-likeness necessary to test this idea. Here we show that the antineoplastic drug carmofur, which is used in the clinic to treat colorectal cancers, is a potent AC inhibitor and that this property is essential to its anti-proliferative effects. Modifications in the chemical scaffold of carmofur yield new AC inhibitors that act synergistically with standard antitumoral drugs to prevent cancer cell proliferation. These findings identify AC as an unexpected target for carmofur, and suggest that this molecule can be used as starting point for the design of novel chemosensitizing agents.
HubMed – drug
Anti-folate combination therapies and their effect on the development of drug resistance in Plasmodium vivax.
Filed under: Drug and Alcohol Rehabilitation
Sci Rep. 2013; 3: 1008
Ding S, Ye R, Zhang D, Sun X, Zhou H, McCutchan TF, Pan W
Can we predict the rise and spread of resistance to multi-drug therapy in a more predictable manner? We raise this question after analyzing over 500 Plasmodium vivax isolates collected from different, geographically isolated regions of China for sequence variation in and around the dhfr and dhps genes. We find: that resistance lineages have arisen at least once in each region; that there appears to have been little movement of parasite populations between these areas; and that highly resistant parasites contain dhfr and dhps alleles that are in linkage disequilibrium. We show a direct relationship between this linkage disequilibrium and a parasite’s fitness in the absence of drug pressure. Such fitness would increase the spread of drug resistant phenotypes and is thus a selectable trait. These conclusions raise questions about the appropriate use of some other drug combinations to prevent and treat infection.
HubMed – drug
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