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

Ullah, Asad; Ashraf, Muhammad; Javeed, Aqeel; Anjum, Aftab Ahmad; Attiq, Ali; Ali, Sarwat

doi:10.1016/j.etap.2016.05.017

Cited by 11 publications

(8 citation statements)

References 30 publications

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“…Our findings are in accordance with other formerly published studies that showed a favorable safety profile for metformin. [54][55][56][57] Although there are other medications, including non-steroidal anti-inflammatory medications (NSAIDs), antidepressants and some neuroleptics that exert a potential antimicrobial effect, 16,58 metformin was the selected medication for this study. It was chosen not only because of its superior efficacy as an adjuvant antibacterial, but also because of its preferred safety profile.…”

Section: Discussionmentioning

confidence: 99%

Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria

Masadeh¹,

Alzoubi²,

Masadeh³

et al. 2021

CPAA

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Introduction: The continuous increase in the incidence of bacterial resistance to existing antibiotics represents a worldwide health burden. A surrogate strategy to combat such crisis is to find compounds that restore the antimicrobial activity of the already existing antibiotics against multidrug resistant bacteria. Metformin is a commonly used antidiabetic medication. It has proven benefits in other diseases including cancer, aging-related and infectious diseases. In this study, the potential effect of metformin as an adjuvant therapy to antibiotics was investigated. Methods: Two multidrug resistant bacterial strains were used; methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33,591) and multidrug resistant Pseudomonas aeruginosa (ATCC BAA-2114). To assess its efficacy, metformin was combined with several antibiotics: levofloxacin, chloramphenicol, rifampicin, ampicillin, and doxycycline. The antibacterial effect of metformin was tested using the micro broth dilution method. The minimum inhibitory concentration (MIC) was also measured. Cytotoxicity studies were also performed on mammalian cells to assess its safety. Results: Metformin exhibited an antibacterial effect when combined with the antibiotics on the two tested strains. It also showed low toxicity on the mammalian cells. Moreover, synergetic studies showed that metformin enhanced the effect of the combined antibiotics, as these combinations provide either a synergistic or additive effect with significant reduction in the MIC. Conclusion:Metformin exerts an adjuvant antibacterial effect; thus, it could be a possible candidate as an adjuvant therapy to reduce antimicrobial resistance.

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Section: Discussionmentioning

confidence: 99%

Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria

Masadeh¹,

Alzoubi²,

Masadeh³

et al. 2021

CPAA

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“…A previous study investigating the combined application of metformin and celecoxib found that together they synergistically inhibited cell proliferation in a concentration-dependent manner. Since this increase in cytotoxicity does not increase DNA damage, this combination can be used to inhibit the growth of malignant cells without any genotoxic or mutational effects at the cellular level [56]. Therefore, combined molecular targeted therapy can be used for certain types of advanced malignancies.…”

Section: Discussionmentioning

confidence: 99%

Novel combination of celecoxib and metformin improves the antitumor effect by inhibiting the growth of Hepatocellular Carcinoma

Hu¹,

Chen²,

Zhang³

et al. 2020

J. Cancer

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Objective: To explore the effect of COX-2 inhibitor celecoxib in combination with metformin on the prevention of Hepatocellular carcinoma (HCC) and the mechanisms involved. Methods: HCC cell lines and an HCC rat model were treated with celecoxib, metformin or a combination of both. Cell viability and tumor formation were measured. Results: In vitro and in vivo studies showed that treatment with a combination of celecoxib and metformin inhibited proliferation of HCC to a greater extent than either treatment alone, by reducing the phosphorylation of MTOR. Conclusion: The study suggested that celecoxib combined with metformin would be more effective for the preventing occurrence of HCC than either treatment alone and this combination of therapy is worthy of further study.

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“…Regarding the mutagenic/clastogenic/recombinogenic potential of MET, literature data are conflicting. Some studies have shown that MET is not genotoxic in vivo or in vitro (ALEISA et al, 2007;ATTIA et al, 2009;AMADOR et al, 2012;MALEK et al, 2015;SANT'ANNA et al, 2013;CHEKI et al, 2016;ULLAH et al, 2016), non-recombinogenic (SANT'ANNA et al, 2013) and may protect from genomic instability (ATTIA et al, 2009;CHEKI et al, 2016;ULLAH et al, 2016). Nevertheless, MET induced genotoxicity in rodent cells in vitro (AMADOR et al, 2012) and in T2DM patients in vivo (HARISHANKAR et al, 2015 (ALEISA et al, 2007;SHETA et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Modulatory effects of Metformin on mutagenicity and epithelial tumor incidence in doxorubicin-treated Drosophila melanogaster

Oliveira¹

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

Cited by 11 publications

References 30 publications

Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria

Metformin as a Potential Adjuvant Antimicrobial Agent Against Multidrug Resistant Bacteria

Novel combination of celecoxib and metformin improves the antitumor effect by inhibiting the growth of Hepatocellular Carcinoma

Modulatory effects of Metformin on mutagenicity and epithelial tumor incidence in doxorubicin-treated Drosophila melanogaster

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