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 language | English |
|---|---|
| Journal | International Journal of Molecular Sciences |
| Volume | 20 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - May 31 2019 |
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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
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 journal › Article
}
TY - JOUR
T1 - Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes
AU - Palombo, Ramona
AU - Caporali, Sabrina
AU - Falconi, Mattia
AU - Iacovelli, Federico
AU - Morozzo Della Rocca, Blasco
AU - Lo Surdo, Alessandro
AU - Campione, Elena
AU - Candi, Eleonora
AU - Melino, Gerry
AU - Bernardini, Sergio
AU - Terrinoni, Alessandro
PY - 2019/5/31
Y1 - 2019/5/31
N2 - 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.
AB - 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.
KW - glycolysis
KW - hexokinase inhibitor
KW - luteolin-7-O-β-d-glucoside
UR - http://www.scopus.com/inward/record.url?scp=85067182817&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067182817&partnerID=8YFLogxK
U2 - 10.3390/ijms20112689
DO - 10.3390/ijms20112689
M3 - Article
C2 - 31159225
AN - SCOPUS:85067182817
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 11
ER -