Enhancement of anti-proliferative activities of Metformin, when combined with Celecoxib, without increasing DNA damage.
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.
Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan. Electronic address: asadullahpharmd@gmail.com.
Asad
A
Ullah
Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Muhammad
M
Ashraf
Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Aqeel
A
Javeed
Department of Microbiology, University of Veterinary and Animal Science, Lahore, Pakistan.
Aftab Ahmad
AA
Anjum
Faculty of Pharmacy, University Kebangsaan Malaysia, Kuala Lampur, Malaysia.
Ali
A
Attiq
Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Sarwat
S
Ali
D000818:Animals; D000068579:Celecoxib / Q000008:administration & dosage / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008687:Metformin / Q000008:administration & dosage / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014709:Vero Cells
D008687:Metformin; D000068579:Celecoxib
Celecoxib; Diabetic malignancies; Metformin; Mutation; Type II diabetes