Metformin May Alter the Metabolic Reprogramming in Cancer Cells by Disrupting the L-Arginine Metabolism: A Preliminary Computational Study.

Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein kinase activation is one of the established mechanisms for metformin's anti-cancer actions. However, it has been suggested that metformin may exert antitumoral effects by the modulation of other master regulators of cellular energy. Here, based on structural and physicochemical criteria, we tested the hypothesis that metformin may act as an antagonist of L-arginine metabolism and other related metabolic pathways. First, we created a database containing different L-arginine-related metabolites and biguanides. After that, comparisons of structural and physicochemical properties were performed employing different cheminformatic tools. Finally, we performed molecular docking simulations using AutoDock 4.2 to compare the affinities and binding modes of biguanides and L-arginine-related metabolites against their corresponding targets. Our results showed that biguanides, especially metformin and buformin, exhibited a moderate-to-high similarity to the metabolites belonging to the urea cycle, polyamine metabolism, and creatine biosynthesis. The predicted affinities and binding modes for biguanides displayed good concordance with those obtained for some L-arginine-related metabolites, including L-arginine and creatine. In conclusion, metabolic reprogramming in cancer cells by metformin and biguanides may be also driven by metabolic disruption of L-arginine and structurally related compounds.

An analysis of unused and expired medications in Mexican households.

BACKGROUND: Unsafe storage of unused medications at home leads to an increased risk of toxicity, accidental childhood poisoning or risk for suicide, whereas an improper disposal of unwanted/expired medications from household raises concern about environmental pollution. OBJECTIVE: The aim of the study was to characterize expired medications collected according to the types of therapeutic groups, pharmaceutical dosage forms, expiration dates and were prescribed or over the counter drugs, and whether they came from Mexican health system or purchased by patients themselves. SETTING: The study was conducted in the metropolitan area of Monterrey during a 12-month period from March 2012 to February 2013. METHOD: Unused/expired drugs were collected according to the collection and disposal of expired medication program instituted by the Department of Health of the State of Nuevo León. Pharmacists and students from The Autonomous University of Nuevo León recorded types of therapeutic groups, total of medicines in each group, among other classification criteria. MAIN OUTCOME MEASURE: The proportion of every collected therapeutic group, type of dosage forms, and expiration date. RESULTS: The amount of medications classified was 22,140 items corresponding to a 30 % of the total collected medications in that period of time; most of them belonged to the non-steroidal anti-inflammatory drugs (16.11 %). According to the pharmaceutical dosage forms, results showed that a high percentage were solid dosage forms (73.39 %), of the total unused/expired medications, most of them were prescription drugs (91 %) which were purchased at private pharmacies. Expiration date of medications ranges from 1995 to 2016, being 2011 the outstanding year (36.66 %). CONCLUSION: Addressing the aspect of unused drug disposition constitutes a challenge for Mexican government, due to health implications related to inadequate disposition. No matter how efficient the programs of collection and disposal of expired drugs are, none of them can collect all unused or expired drugs, that is the reason why the best approach might be to prevent this need.