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AKR1B10 is an NADPH-dependent reductase that plays an important function in several physiological reactions such as the conversion of retinal to retinol, reduction of isoprenyl aldehydes, and biotransformation of procarcinogens and drugs. A growing body of evidence points to the important role of the enzyme in the development of several types of cancer (e.g., breast, hepatocellular), in which it is highly overexpressed. AKR1B10 is regarded as a therapeutic target for the treatment of these diseases, and potent and specific inhibitors may be promising therapeutic agents. Several inhibitors of AKR1B10 have been described, but the area of natural plant products has been investigated sparingly. In the present study almost 40 diverse phenolic compounds and alkaloids were examined for their ability to inhibit the recombinant AKR1B10 enzyme. The most potent inhibitors-apigenin, luteolin, and 7-hydroxyflavone-were further characterized in terms of IC50, selectivity, and mode of action. Molecular docking studies were also conducted, which identified putative binding residues important for the interaction. In addition, cellular studies demonstrated a significant inhibition of the AKR1B10-mediated reduction of daunorubicin in intact cells by these inhibitors without a considerable cytotoxic effect. Although these compounds are moderately potent and selective inhibitors of AKR1B10, they constitute a new structural type of AKR1B10 inhibitor and may serve as a template for the development of better inhibitors.

MeSH
aldehydreduktasa antagonisté a inhibitory účinky léků MeSH
apigenin farmakologie MeSH
daunomycin farmakologie MeSH
flavonoidy farmakologie MeSH
flavony chemie farmakologie MeSH
HCT116 buňky MeSH
inhibitory enzymů chemie MeSH
lidé MeSH
luteolin farmakologie MeSH
molekulární konformace MeSH
molekulární struktura MeSH
nádory farmakoterapie MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

Chronické ochorenia žíl dolných končatín v ambulancii všeobecného lekára pre dospelých
[Chronic venous diseases of the lower limbs in a general practitioner's surgery]

Vaverková, Iveta
Autor Vaverková, Iveta Ambulancia všeobecného lekára pre dospelých, Bratislava

Postgraduální medicína. 2013 ; 15 (9) : 963-968.

Postgraduální med.
ISSN 1212-4184
Medvik
Zdroj

Chronické venózne ochorenie patrí medzi chronické civilizačné ochorenia s možnými závažnými zdravotnými následkami a zároveň predstavuje aj významný socio-ekonomický problém v spoločnosti. Rozhodujúcu úlohu v etiopatogenéze zohrávajú endotelová dysfunkcia, aktivácia leukocytov a chronická zápalová reakcia cievnej steny. Následkom sú venózna hypertenzia, vznik varixov a trofických zmien kože. Liečba CHVO musí byť dlhodobá a komplexná. Pre jej úspešnosť je potrebná aktívna spolupráca pacienta.

Chronic venous diseases of the lower limbs in a general practitioner's surgery Chronic venous diseases belong among chronic civilisation diseases with possible serious consequences and they also represent a significant socio-economic problem in the society. The decisive role in their aetiopathogenesis is played by endothelium dysfunction, leukocyte activation and chronic inflammatory reaction of the venous wall. The consequences of that are venous hypertension, varicose veins and trophic skin changes. Treatment needs to be complex and long-term. Active cooperation on the patient's part is essential for its success.

Článek

Antiproliferative and antiangiogenic effects of flavone eupatorin, an active constituent of chloroform extract of Orthosiphon stamineus leaves

Fitoterapia. 2012 ; 83 (6) : 1000-7.

Fitoterapia (Milano)
ISSN 1873-6971
Medvik
Zdroj

Flavone eupatorin is one of the constituents of Orthosiphon stamineus, a medicinal herb used in folk medicine in South East Asia for treatment of various disorders. In our study, we investigated the antiproliferative properties of a chloroform extract of the leaves of O. stamineus and of pure eupatorin. The compound was able to reduce the number of viable cancer cells to the same extent as the extract, with IC(50) values in micromolar range. Moreover, both the eupatorin standard and the extract caused cells to arrest in the G2/M phase of the cell cycle. This clearly demonstrates that eupatorin contributes significantly to the overall extract activity. Induction of mitotic catastrophe, accompanied by key molecular events defining apoptosis, is the mechanism of eupatorin-induced cell death. Importantly, eupatorin (at the doses cytotoxic to cancer cells) did not kill normal cells; it only limited migration of HUVEC endothelial cells and their ability to create tubes. The ability of eupatorin to nonspecifically inhibit many protein kinases was proven and is the probable cause of its cellular effects. In summary, eupatorin emerges as a promising agent in anticancer research.