Flavones Inhibit the Activity of AKR1B10, a Promising Therapeutic Target for Cancer Treatment

Zemanová, Lucie; Hofman, Jakub; Novotná, Eva; Musílek, Kamil; Lundová, Tereza; Havránková, Jana; Hošťálková, Anna; Chlebek, Jakub; Cahlíková, Lucie; Wsól, Vladimı́r

doi:10.1021/acs.jnatprod.5b00616

Cited by 31 publications

(18 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plant extracts and natural compounds including inhibitors of AKR1B1 and other members of the aldo‐keto reductase superfamily have been studied in an effort to discover new agents for the therapeutic treatment of such medical problems as inflammation, the complications of chronic diabetes and other problems involving aldo‐keto reductases (Zemanova et al, ; Koo et al, ; Karasu et al, ;). The inhibition of AKR1B1 has been found to reduce the inflammation of tissues (Srivastava et al, ; Yadav et al, ; Yadav et al, ; Kador et al, ).…”

Section: Resultsmentioning

confidence: 99%

Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells

et al. 2017

View full text Add to dashboard Cite

The human intracellular enzyme AKR1B1 belongs to the aldo-keto reductase superfamily. The AKR1B1-catalyzed reduction of aldehydes is part of the intracellular inflammatory pathway leading to the activation of NF-κB and the expression of pro-inflammatory genes. The present study is aimed at determining the inhibition of AKR1B1 brought about by an extract of artichoke leaves (bracts), and the effects of this extract and three participating compounds on the expression of AKR1B1, COX-2, and MMP-2 proteins in THP-1 cells. It seeks to identify the ability of the test substances to modulate the lipopolysaccharide (LPS)-induced activation of NF-κB in cells and the intracellular oxidant effect of test substances after incubation with LPS. Low concentrations of the extract inhibit the enzyme AKR1B1. After stimulation by LPS, the extract attenuated the activity of NF-κB in THP-1 cells, but no changes in the expression of AKR1B1 were recorded. The extract diminished the expression of the inflammation-related enzymes COX-2 and MMP-2, probably by inhibiting the activity of NF-κB. The extract significantly diminished the intracellular reactive oxygen species after a brief LPS incubation, which may also have reduced intracellular inflammation. The diminished activity of NF-κB in the cells could be linked to the inhibition of the activity of AKR1B1. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

Section: Resultsmentioning

confidence: 99%

Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Quercetin was reported to inhibit the activity of AKR1B10 in catalyzing the reduction of retinal to retinol and the reduction of isoprenyl aldehydes (Zemanova et al, 2015). Hence, in addition to ascorbic acid, quercetin might potentiate the anti-tumor properties of BLE by down-regulating the expression of ADH4 , AKR1B10 and AKR1C2 , thus preventing the degradation of methylglyoxal.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

Kong

Aziz

Razali

et al. 2016

PeerJ

View full text Add to dashboard Cite

BackgroundBarringtonia racemosa is a medicinal plant belonging to the Lecythidaceae family. The water extract of B. racemosa leaf (BLE) has been shown to be rich in polyphenols. Despite the diverse medicinal properties of B. racemosa, information on its major biological effects and the underlying molecular mechanisms are still lacking.MethodsIn this study, the effect of the antioxidant-rich BLE on gene expression in HepG2 cells was investigated using microarray analysis in order to shed more light on the molecular mechanism associated with the medicinal properties of the plant.ResultsMicroarray analysis showed that a total of 138 genes were significantly altered in response to BLE treatment (p < 0.05) with a fold change difference of at least 1.5. SERPINE1 was the most significantly up-regulated gene at 2.8-fold while HAMP was the most significantly down-regulated gene at 6.5-fold. Ingenuity Pathways Analysis (IPA) revealed that “Cancer, cell death and survival, cellular movement” was the top network affected by the BLE with a score of 44. The top five canonical pathways associated with BLE were Methylglyoxal Degradation III followed by VDR/RXR activation, TR/RXR activation, PXR/RXR activation and gluconeogenesis. The expression of genes that encode for enzymes involved in methylglyoxal degradation (ADH4, AKR1B10 and AKR1C2) and glycolytic process (ENO3, ALDOC and SLC2A1) was significantly regulated. Owing to the Warburg effect, aerobic glycolysis in cancer cells may increase the level of methylglyoxal, a cytotoxic compound.ConclusionsBLE has the potential to be developed into a novel chemopreventive agent provided that the cytotoxic effects related to methylglyoxal accumulation are minimized in normal cells that rely on aerobic glycolysis for energy supply.

show abstract

“…Flavones could be used as a new structural type of AKR1B10 inhibitor [78]. The strongest flavones, apigenin ( 12 ), luteolin ( 13 ), and 7-hydroxyflavone ( 14 ), can significantly inhibit reductase activities of human recombinant AKR1B10.…”

Section: Akr1b10 Inhibitorsmentioning

confidence: 99%

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Huang¹,

He²,

Luo³

et al. 2016

PRA

View full text Add to dashboard Cite

Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function.

show abstract

Flavones Inhibit the Activity of AKR1B10, a Promising Therapeutic Target for Cancer Treatment

Cited by 31 publications

References 57 publications

Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells

Artichoke Leaf Extract Inhibits AKR1B1 and Reduces NF-κB Activity in Human Leukemic Cells

Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Contact Info

Product

Resources

About