In vitro combinatory cytotoxicity of hepatocarcinogenic asarone isomers and flavonoids

Uebel, Thomas; Wilken, Markus; Vu, Hung V.; Esselen, Melanie

doi:10.1016/j.tiv.2019.04.029

Cited by 8 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest that the cytotoxicity of the asarones correlated with protein modification resulting from the metabolic activation of the asarones and with the efficiency of the bioactivation. We also noticed that αA showed greater cytotoxicity than βA to HepG2 28,29 and Thle-2 30 cells. The inconsistency with our observation possibly results from deficient cytochrome P450 proteins in the two cell lines.…”

Section: Discussionmentioning

confidence: 59%

Configurational Alteration Results in Change in Hepatotoxicity of Asarone

Zhao

Wang

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

α-Asarone (αA) and β-asarone (βA) are often used as flavoring agents for alcoholic beverages and food supplements. They possess a double bond in the side chain with different configurations. Double bonds are a class of alert chemical group, due to their metabolic epoxidation to the corresponding epoxides eliciting liver injury. Little is known about changes of configuration on metabolic activation and related toxicity. Here, we report the insight into the mechanisms of hepatotoxicity of asarone with different configurations. In vitro and in vivo comparative studies demonstrated βA displayed higher metabolic activation effectiveness. Apparently, the major metabolic pathway of βA underwent epoxidation at C-1′ and C-2′, while αA was mainly metabolized to the corresponding alcohol resulting from the hydroxylation of C-3′. CYP1A2 dominated the metabolism of αA and βA. The molecular simulation studies showed that the orientation of βA at the active site of CYP1A2 favored the epoxidation of βA over that of αA. These findings not only remind us that configuration is another important factor for toxicities but also facilitate the understanding of the mechanisms of toxic action of asarone. Additionally, these findings would benefit the risk assessment of αA and βA exposure from foods.

show abstract

Section: Discussionmentioning

confidence: 59%

Configurational Alteration Results in Change in Hepatotoxicity of Asarone

Zhao

Wang

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“…Combinatory antiprolifetarive and palliative effects have been reported for flavonoids on clinic symptoms associated with all therapeutical antitumor drugs, such as nausea, vomiting, diarrhea, mucositis, kidney problems, and peripherial neuropathic pain (Uebel et al 2019;Fernández et al 2021). In addition, the protective effect of flavonoids in radiotherapy has also been demonstrated (Wang et al 2020;Wu et al 2023).…”

Section: Resultsmentioning

confidence: 99%

Cytotoxicity of Salvigenin from Asterohyptis stellulata in Combination with Clinical Drugs Against Colorectal Cancer

Rojas-Castaño,

Hernández-Rojas,

Pereda-Miranda

et al. 2024

Rev. Bras. Farmacogn.

View full text Add to dashboard Cite

Flavonoids, abundant polyphenols in various plant-based sources, exhibit diverse health benefits, particularly in cancer prevention and treatment, attributed to their ability to mitigate oxidative stress. Salvigenin, a naturally occurring trimethoxylated flavone from the aerial parts of Asterohyptis stellulata Epling, Lamiaceae, has gained attention for its potential synergistic effects with conventional anticancer drugs. The present study describes the evaluation of salvigenin, a non-cytotoxic flavone (IC50 > 50 µM), in combination assays with clinical drugs in human colon carcinoma cells (HCT-116), which revealed significant differences as compared to single salvigenin treatments. Remarkably, IC50 values of 1.8 and 1.5 µM for the combination of salvigenin with sublethal concentrations of podophyllotoxin and colchicine (0.008 µM), respectively, were observed, indicating an enhancement in its cytotoxicity effectiveness. These findings emphasize the potential of salvigenin-based combination therapies as a promising strategy for colorectal cancer treatment, offering improved therapeutic results with reduced clinical drug doses and associated side effects. Graphical Abstract

show abstract

“…Iwata et al (1997) illustrate this contrast in their work with (Z)-and (E)-3-hydroxy-3'methylchalcone, where the (Z)-isomer inhibited proliferation of HGC-27 cells nearly twice as much than the (E)-isomer. Recently, Ubel et al (2019) showed different IC 50 values for α and β-asarone in HepG2 cells. The authors also demonstrated the synergistic effect reached by different proportioned mixtures of these isomers.…”

Section: Discussionmentioning

confidence: 99%

The Brazilian octocoral Phyllogorgia dilatata as a source of cytotoxic compounds

Fagundes

Macedo

Rigato

et al. 2021

An. Acad. Bras. Ciênc.

View full text Add to dashboard Cite

The extensive marine biodiversity has proved to be a promising source of substances with biomedical potential. In this study, the cytotoxicity of the Brazilian octocoral Phyllogorgia dilatata (Gorgoniidae) was evaluated against two tumor cell lines and three bacterial strains. The methanol/dichloromethane crude extract presented no antibacterial activity up to the highest concentration tested (512 µg/mL), however it revealed a noteworthy antiproliferative effect against HCT-116 (80%) and MCF-7 (54%) cell lines at 50 μg/mL. Therefore, guided by the cytotoxic activity, a multistep chemical fractionation of the extract provided the subfraction 5 (PDPH2-5) with IC 50 values of 3.18 and 17.80 μg/mL against HCT-116 and MCF-7, respectively. The LC-HRMS/MS analysis of PDPH2-5 showed ions of m/z 219.1742 and 219.1743, characterized as (E,E) and (Z,E) germacrone, after a LC-DAD-SPE/NMR analysis of the hexanic fraction and comparisons of NMR data with the literature. Previously reported assessments to the cytotoxic activity of the (E,E)-diastereoisomer disclosed higher IC 50 values than that obtained for the PDPH2-5 fraction, suggesting, herein, a potentiated effect of the diastereoisomeric mixture. Such remark encourage further bioactivity studies with stereoisomer mixtures and reduce the urge for compound isolation.

show abstract

In vitro combinatory cytotoxicity of hepatocarcinogenic asarone isomers and flavonoids

Cited by 8 publications

References 44 publications

Configurational Alteration Results in Change in Hepatotoxicity of Asarone

Configurational Alteration Results in Change in Hepatotoxicity of Asarone

Cytotoxicity of Salvigenin from Asterohyptis stellulata in Combination with Clinical Drugs Against Colorectal Cancer

The Brazilian octocoral Phyllogorgia dilatata as a source of cytotoxic compounds

Contact Info

Product

Resources

About