The Modulation of Phase II Drug-Metabolizing Enzymes in Proliferating and Differentiated CaCo-2 Cells by Hop-Derived Prenylflavonoids

Lněničková, Kateřina; Šadibolová, Michaela; Matoušková, Petra; Szotáková, Barbora; Skálová, Lenka; Boušová, Iva

doi:10.3390/nu12072138

Cited by 14 publications

(17 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GSTA1-1 is highly expressed in many non-small-cell lung cancer cell lines and plays a crucial role in the development of anticancer drug resistance. Its downregulation leads to suppression of tumor growth and the induction of cell apoptosis [39,40]. Therefore, the downregulation of the GSTA1-1 mRNA expression caused by fisetin in proliferating CaCo-2 cells, observed in the present work, suggests a synergistic function of fisetin regarding the suppression and chemosensitization of cancer cells.…”

Section: The Effect Of Fisetin On Hgsta1-1 Expression and Inhibition supporting

confidence: 61%

The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

et al. 2021

View full text Add to dashboard Cite

Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that are involved in the development of the multidrug resistance (MDR) mechanism in cancer cells and therefore affect the clinical outcome of cancer chemotherapy. The discovery of nontoxic natural compounds as inhibitors for GSTs is a promising approach for chemosensitizing and reversing MDR. Fisetin (7,3′,4′-flavon-3-ol) is a plant flavonol present in many plants and fruits. In the present work, the interaction of fisetin with human glutathione transferase A1-1 (hGSTA1-1) was investigated. Kinetic analysis revealed that fisetin is a reversible inhibitor for hGSTA1-1 with IC50 1.2 ± 0.1 μΜ. It functions as a mixed-type inhibitor toward glutathione (GSH) and as a noncompetitive inhibitor toward the electrophile substrate 1-chloro-2,4-dinitrobenzene (CDNB). In silico molecular modeling and docking predicted that fisetin binds at a distinct location, in the solvent channel of the enzyme, and occupies the entrance of the substrate-binding sites. Treatment of proliferating human epithelial colorectal adenocarcinoma cells (CaCo-2) with fisetin causes a reduction in the expression of hGSTA1-1 at the mRNA and protein levels. In addition, fisetin inhibits GST activity in CaCo-2 cell crude extract with an IC50 (2.5 ± 0.1 μΜ), comparable to that measured using purified recombinant hGSTA1-1. These actions of fisetin can provide a synergistic role toward the suppression and chemosensitization of cancer cells. The results of the present study provide insights into the development of safe and effective GST-targeted cancer chemosensitizers.

show abstract

Section: The Effect Of Fisetin On Hgsta1-1 Expression and Inhibition supporting

confidence: 61%

The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The differences in the effect of xanthohumol and the other hop-derived prenylflavonoids in proliferating and differentiated colorectal cancer cells (CaCo-2 cells) were demonstrated. In the latter, expression of phase II enzymes also showed specificity toward their isozymes, namely GST [ 42 ].…”

Section: Phytochemicals As Modulators Of Nrf2 and Nf-kb Signaling Pathwaymentioning

confidence: 99%

Modulation of Nrf2 and NF-κB Signaling Pathways by Naturally Occurring Compounds in Relation to Cancer Prevention and Therapy. Are Combinations Better Than Single Compounds?

Krajka‐Kuźniak¹,

Baer‐Dubowska²

2021

IJMS

View full text Add to dashboard Cite

Nrf2 (nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor–kappa B) signaling pathways play a central role in suppressing or inducing inflammation and angiogenesis processes. Therefore, they are involved in many steps of carcinogenesis through cooperation with multiple signaling molecules and pathways. Targeting both transcription factors simultaneously may be considered an equally important strategy for cancer chemoprevention and therapy. Several hundreds of phytochemicals, mainly edible plant and vegetable components, were shown to activate Nrf2 and mediate antioxidant response. A similar number of phytochemicals was revealed to affect NF-κB. While activation of Nrf2 and inhibition of NF-κB may protect normal cells against cancer initiation and promotion, enhanced expression and activation in cancer cells may lead to resistance to conventional chemo- or radiotherapy. Most phytochemicals, through different mechanisms, activate Nrf2, but others, such as luteolin, can act as inhibitors of both Nrf2 and NF-κB. Despite many experimental data confirming the above mechanisms currently, limited evidence exists demonstrating such activity in humans. Combinations of phytochemicals resembling that in a natural food matrix but allowing higher concentrations may improve their modulating effect on Nrf2 and NF-κB and ultimately cancer prevention and therapy. This review presents the current knowledge on the effect of selected phytochemicals and their combinations on Nrf2 and NF-κB activities in the above context.

show abstract

“…Taking into account the conclusions of Ambroz’s study [ 49 ], which reports antagonistic effects on concomitant administration of xanthohumol/chemotherapy, it was concluded that administration should be staged, in order to avoid decreasing the efficacy of the chemotherapeutics. It should be noted that other studies confirmed the cytotoxic action of other prenylflavonoids in hops on colonic proliferative cells, but xanthohumol had the most active contribution [ 50 ].…”

Section: Hops Antioxidants and Cancermentioning

confidence: 86%

Antioxidants in Hops: Bioavailability, Health Effects and Perspectives for New Products

Zugravu

Bohîlțea

Salmen³

et al. 2022

Antioxidants

View full text Add to dashboard Cite

Hop plant (Humulus lupulus L.) has been used by humans for ages, presumably first as a herbal remedy, then in the manufacturing of different products, from which beer is the most largely consumed. Female hops cones have different useful chemical compounds, an important class being antioxidants, mainly polyphenols. This narrative review describes the main antioxidants in hops, their bioavailability and biological effects, and the results obtained by now in the primary and secondary prevention of several non-communicable diseases, such as the metabolic syndrome related diseases and oncology. This article presents in vitro and in vivo data in order to better understand what was accomplished in terms of knowledge and practice, and what needs to be clarified by additional studies, mainly regarding xantohumol and its derivates, as well as regarding the bitter acids of hops. The multiple protective effects found by different studies are hindered up to now by the low bioavailability of some of the main antioxidants in hops. However, there are new promising products with important health effects and perspectives of use as food supplements, in a market where consumers increasingly search for products originating directly from plants.

show abstract

The Modulation of Phase II Drug-Metabolizing Enzymes in Proliferating and Differentiated CaCo-2 Cells by Hop-Derived Prenylflavonoids

Cited by 14 publications

References 52 publications

The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

Modulation of Nrf2 and NF-κB Signaling Pathways by Naturally Occurring Compounds in Relation to Cancer Prevention and Therapy. Are Combinations Better Than Single Compounds?

Antioxidants in Hops: Bioavailability, Health Effects and Perspectives for New Products

Contact Info

Product

Resources

About