NDLI: Enhancement of anti-proliferative activities of Metformin, when combined with Celecoxib, without increasing DNA damage.

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Enhancement of anti-proliferative activities of Metformin, when combined with Celecoxib, without increasing DNA damage.

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Enhancement of anti-proliferative activities of Metformin, when combined with Celecoxib, without increasing DNA damage.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ullah, Asad Ashraf, Muhammad Javeed, Aqeel Anjum, Aftab Ahmad Attiq, Ali Ali, Sarwat
Description	Author Affiliation: Ullah A ( Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan. Electronic address: asadullahpharmd@gmail.com.); Ashraf M ( Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.); Javeed A ( Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.); Anjum AA ( Department of Microbiology, University of Veterinary and Animal Science, Lahore, Pakistan.); Attiq A ( Faculty of Pharmacy, University Kebangsaan Malaysia, Kuala Lampur, Malaysia.); Ali S ( Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.)
Abstract	Pathophysiological changes in diabetes like hyperglycemia, oxidative stress, insulin resistance and compensatory hyperinsulinemia predispose cells to malignant transformation and damage DNA repair mechanism. This study was designed to explore the potential synergistic toxic effects of anti-diabetic drug (Metformin), and an analgesic drug (Celecoxib) at cellular level. MTT assay run on Vero cell line revealed that the combinations of Metformin and Celecoxib augment the anti-proliferative effects, whereas Single cell gel electrophoresis spotlighted that Metformin produce non-significant DNA damage with the threshold concentration of 400µg/ml in peripheral blood mononuclear cells (lymphocytes and monocytes), while Celecoxib produced significant (P<0.05) DNA damage (class III comets) above the concentration of 75µg/ml, however the DNA damage or DNA tail protrusions by combinations of both drugs were less than what was observed with Celecoxib alone. Metformin or Celecoxib did not appear mutagenic against any mutant strains (TA 100 and TA 98) but their combination exhibited slight mutagenicity at much higher concentration. The results obtained at concentrations higher than the therapeutic level of drugs and reflect that Metformin in combination with Celecoxib synergistically inhibits the cell proliferation in a concentration dependent pattern. Since, this increase in cytotoxicity did not confer an increase in DNA damage; this combination could be adopted to inhibit the growth of malignant cell without producing any genotoxic or mutagenic effects at cellular level.
File Format	HTM / HTML
ISSN	13826689
Journal	Environmental Toxicology and Pharmacology
Volume Number	45
e-ISSN	18727077
Language	English
Publisher	Elsevier
Publisher Date	2016-07-01
Publisher Place	Netherlands
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Environmental Health Discipline Pharmacology
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology Pharmacology

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