Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes

Ramona Palombo, Sabrina Caporali, Mattia Falconi, Federico Iacovelli, Blasco Morozzo Della Rocca, Alessandro Lo Surdo, Elena Campione, Eleonora Candi, Gerry Melino, Sergio Bernardini, Alessandro Terrinoni

Research output: Contribution to journalArticle

Abstract

Flavonoids have been demonstrated to affect the activity of many mammalian enzyme systems. Their functional phenolic groups are able to mediate antioxidant effects by scavenging free radicals. Molecules of this class have been found able to modulate the activity of kinases, phospholipase A2, cyclooxygenases, lipoxygenase, glutathione S-transferase, and many others. Recently, it has been demonstrated that luteolin, in the form of Luteolin-7-O-β-d-glucoside (LUT-7G) is able to induce the keratinocyte differentiation process in vitro. This flavonoid is able to counteract the proliferative effects of IL-22/IL6 pathway by the inhibition of STAT3 activity also in vivo in a psoriatic mouse model. Observations on energy metabolism changes of differentiating cells led us to perform a complete metabolomics analysis using human primary keratinocytes treated with LUT-7G. Our results show that LUT-7G, is not only able to impair the nuclear translocation of STAT3, but it also blocks the energy metabolism pathway, depressing the glycolytic and Krebs pathway by the inhibition of hexokinase 2 activity. These data confirm that LUT-7G can be proposed as a potential candidate for the treatment of inflammatory and proliferative diseases, but its role as a hexokinase 2 (HEK2) inhibitor opens new perspectives in nutritional science, and especially in cancer therapy, in which the inhibition of the Warburg effect could be relevant.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number11
DOIs
Publication statusPublished - May 31 2019

Fingerprint

hexokinase
Luteolin
glucosides
Hexokinase
Glucosides
Keratinocytes
Flavonoids
metabolism
Energy Metabolism
Nutritional Sciences
glutathione
Metabolomics
Lipoxygenase
energy
Phospholipases A2
Scavenging
scavenging
antioxidants
Prostaglandin-Endoperoxide Synthases
Glutathione Transferase

Keywords

  • glycolysis
  • hexokinase inhibitor
  • luteolin-7-O-β-d-glucoside

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Palombo, R., Caporali, S., Falconi, M., Iacovelli, F., Morozzo Della Rocca, B., Lo Surdo, A., ... Terrinoni, A. (2019). Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes. International Journal of Molecular Sciences, 20(11). https://doi.org/10.3390/ijms20112689

Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes. / Palombo, Ramona; Caporali, Sabrina; Falconi, Mattia; Iacovelli, Federico; Morozzo Della Rocca, Blasco; Lo Surdo, Alessandro; Campione, Elena; Candi, Eleonora; Melino, Gerry; Bernardini, Sergio; Terrinoni, Alessandro.

In: International Journal of Molecular Sciences, Vol. 20, No. 11, 31.05.2019.

Research output: Contribution to journalArticle

Palombo, R, Caporali, S, Falconi, M, Iacovelli, F, Morozzo Della Rocca, B, Lo Surdo, A, Campione, E, Candi, E, Melino, G, Bernardini, S & Terrinoni, A 2019, 'Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes', International Journal of Molecular Sciences, vol. 20, no. 11. https://doi.org/10.3390/ijms20112689
Palombo, Ramona ; Caporali, Sabrina ; Falconi, Mattia ; Iacovelli, Federico ; Morozzo Della Rocca, Blasco ; Lo Surdo, Alessandro ; Campione, Elena ; Candi, Eleonora ; Melino, Gerry ; Bernardini, Sergio ; Terrinoni, Alessandro. / Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 11.
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