Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytes in vitro via mTOR-signaling pathway

Pharmaceutical Biology

Volumn 54, Issue 7, 2016, Pages 1173-1178

  Liu, Ying ^a   Yang, Fan ^a   Ma, Weiyuan ^b   Sun, Qing ^b  

^a THE SECOND HOSPITAL OF SHANDONG UNIVERSITY   (China)

^b SHANDONG UNIVERSITY   (China)

Author keywords

Apoptosis; HaCaT cells; psoriasis

Indexed keywords

3 (4,5 DIMETHYL 2 THIAZOLYL) 2,5 DIPHENYLTETRAZOLIUM BROMIDE; INTERLEUKIN 6; MAMMALIAN TARGET OF RAPAMYCIN; METFORMIN; S6 KINASE; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN; ANTIINFLAMMATORY AGENT; AUTACOID; CYTOKINE; IL6 PROTEIN, HUMAN; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE; TUMOR NECROSIS FACTOR; VASCULOTROPIN A;

ANTIINFLAMMATORY ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL LINE; CANCER INHIBITION; CELL COUNT; CELL PROLIFERATION; CONTROLLED STUDY; DOSE RESPONSE; ENZYME INHIBITION; ENZYME LINKED IMMUNOSORBENT ASSAY; ENZYME PHOSPHORYLATION; FLOW CYTOMETRY; HACAT CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; INCUBATION TIME; KERATINOCYTE; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; SURVIVAL RATE; WESTERN BLOTTING; CELL CYCLE CHECKPOINT; CELL LINE; DRUG EFFECTS; ENZYMOLOGY; METABOLISM; PATHOLOGY; PHOSPHORYLATION; TIME FACTOR;

ANTI-INFLAMMATORY AGENTS; APOPTOSIS; CELL CYCLE CHECKPOINTS; CELL LINE; CELL PROLIFERATION; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INFLAMMATION MEDIATORS; INTERLEUKIN-6; KERATINOCYTES; METFORMIN; PHOSPHORYLATION; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SIGNAL TRANSDUCTION; TIME FACTORS; TOR SERINE-THREONINE KINASES; TUMOR NECROSIS FACTOR-ALPHA; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84940093983     PISSN: 13880209     EISSN: 17445116     Source Type: Journal    
DOI: 10.3109/13880209.2015.1057652     Document Type: Article

References (27)

1. A.G.Abdou, H.M.Hanout. (2008). Evaluation of survivin and NF-kappaB in psoriasis, an immunohistochemical study. J Cutan Pathol 35:445–51
2. I.Ben Sahra, C.Regazzetti, G.Robert,. (2011). Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res 71:4366–72
3. P.Boukamp, R.T.Petrussevska, D.Breitkreutz,. (1988). Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106:761–71
4. Y.B.Brauchli, S.S.Jick, F.Curtin,. (2008). Association between use of thiazolidinediones or other oral antidiabetics and psoriasis: A population based case–control study. J Am Acad Dermatol 58:421–9
5. C.Buerger, B.Malisiewicz, A.Eiser,. (2013). mTOR and its downstream signalling components are activated in psoriatic skin. Br J Dermatol 169:156–9
6. Y.K.Choi, K.G.Park. (2013). Metabolic roles of AMPK and metformin in cancer cells. Mol Cells 36:279–87
7. E.Frigerio, M.D.Colombo, C.Franchi. (2007). Severe psoriasis treated with a new macrolide: Everolimus. Br J Dermatol 156:372–4
8. T.Huang, X.Lin, X.Meng. (2014). Phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin pathway in psoriasis pathogenesis. A potential therapeutic target? Acta Derm Venereol 94:371–9.
9. B.B.Kahn, T.Alquier, D.Caning,. (2005). AMP activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25
10. J.Karar, A.Maity. (2011). PI3K/AKT/mTOR Pathway in angiogenesis. Front Mol Neurosci 2011;4:51. doi: 10.3389/fnmol.2011.00051
11. A.H.Kirsch, V.Riegelbauer, A.Tagwerker,. (2012). The mTOR-inhibitor rapamycin mediates proteinuria in nephrotoxic serum nephritis by activating the innate immune response. Am J Physiol Renal Physiol 303:569–75
12. A.Leone, E.Di Gennaro, F.Bruzzese,. (2014). New perspective for an old antidiabetic drug: Metformin as anticancer agent. Cancer Treat Res 159:355–76
13. W.Li, W.Ma, H.Zhong,. (2014). Metformin inhibits proliferation of human keratinocytes through a mechanism associated with activation of the MAPK signaling pathway. Exp Ther Med 7:389–92
14. A.Mitra, S.K.Raychaudhuri, S.P.Raychaudhuri. (2012). IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine 60:38–42
15. F.O.Nestle, D.H.Kaplan, J.Barker. (2009). Psoriasis. N Engl J Med 361:496–509
16. A.D.Ormerod, S.A.Shah, P.Copeland,. (2005). Treatment of psoriasis with topical sirolimus: Preclinical development and a randomized, double-blind trial. Br J Dermatol 152:758–64
17. M.Pollak. (2010). Metformin and other biguanides in oncology: Advancing the research agenda. Cancer Prev Res (Phila) 3:1060–5
18. S.Reitamo, P.Spuls, B.Sassolas,. Sirolimu European Psoriasis Study Group. (2001) Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: A randomized controlled trial. Br J Dermatol 145:438–45
19. G.A.Soliman. (2013). The role of mechanistic target of rapamycin (mTOR) complexes signaling in the immune responses. Nutrients 5:2231–57
20. M.Stein, A.Bernd, A.Ramirez-Bosca,. (1997). Measurement of anti-inflammatory effects of glucocorticoids on human keratinocytes in vitro. Comparison of normal human keratinocytes with the keratinocyte cell line HaCaT. Arzneimittelforschung 47:1266–70
21. Y.Storozhuk, S.N.Hopmans, T.Sanli,. (2013). Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer 108:2021–32
22. G.Taubes. (2012). Cancer research. Cancer prevention with a diabetes pill? Science. 335:29
23. X.W.Wang, Y.J.Zhang. (2014). Targeting mTOR network in colorectal cancer therapy. World J Gastroenterolb 20:4178–88
24. K.C.Wei, P.C.Lai. (2015). Combination of everolimus and tacrolimus: A potentially effective regimen for recalcitrant psoriasis. Dermatol Ther 28:25–7
25. T.Weichhart, M.D.Säemann. (2008). The PI3K/Akt/mTOR pathway in innate immune cells: Emerging therapeutic applications. Ann Rheum Dis 67:iii70–4
26. C.Y.Wu, J.J.Shieh, J.L.Shen,. (2015). Association between antidiabetic drugs and psoriasis risk in diabetic patients: Results from a nationwide nested case-control study in Taiwan. J Am Acad Dermatol 72:123–30
27. J.Zhang, W.Y.Ma. (2014). Nerve growth factor regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes via PI3K/mTOR pathway. Genet Mol Res 13:9324–35