Potential Assessment of UGT2B17 Inhibition by Salicylic Acid in Human Supersomes In Vitro

Salhab, Hassan; Naughton, Declan P.; Barker, James

doi:10.3390/molecules26154410

Cited by 3 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and UGT2B17, as the major enzymes involved in glucuronidation of androgens [43]. UGT2B15 protein level decreases in prostate cancer compared to benign hyperplasia and the protein is further reduced in hormone resistant form of prostate cancer and is as low as to be measured in metastasis state [44].…”

Section: Discussionmentioning

confidence: 99%

Untitled

2022

Journal of Bioinformatics and Comparative Genomics

View full text Add to dashboard Cite

After lung cancer, prostate cancer has the highest mortality rate. Early and accurate diagnosis of this heterogeneous cancer promises more effective treatment. At present biopsy is the only definitive method of diagnosing the disease. Many gene loci are associated with increased susceptibility to this cancer. Here, the relationship between tumor necrosis factor alpha (TNF-α) gene variants and glucuronidation pathway gene variants with increased risk of prostate cancer in a population of Iranian men has been investigated. Materials and methods:Blood samples were collected from 360 men including 120 healthy, 120 with benign prostate hyperplasia (BPH), and 120 patients with prostate cancer (PCa). DNA was extracted and tested for each variant with specific primers and PCR based methods. Data were analyzed using agarose and polyacrylamide gel electrophoresis, SPSS software, SNP Stats and Student's t-test.Results: UGT2B17 and UGT2B15 polymorphisms were associated with BPH in comparison to the control group (P value = <0.0001 and P value = 0.007). The only significant association in the cancer group was between G Score and UGT2B15, so that 90% of patients with PCa and G score less than or equal to 6, had GG genotype (0.01). Other variants had no significant relationship with the cause of the disease. Ins Del G haplotype was more common in BPH compared to the control group (P value = 0.011).

show abstract

Section: Discussionmentioning

confidence: 99%

Untitled

2022

Journal of Bioinformatics and Comparative Genomics

View full text Add to dashboard Cite

show abstract

“…Imatinib has also been purposed as a platelet-derived growth factor receptor inhibitor, however in clinical trials, the treatment proved ineffective for PCa patients (169). Recently however, salicylic acid has been discovered as an uncompetitive inhibitor of UGT2B17 (170). This avenue could be explored for the treatment of AR-V7expressing CRPC.…”

Section: Ugt2b17mentioning

confidence: 99%

A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer

et al. 2023

View full text Add to dashboard Cite

Persistent androgen receptor (AR) signalling is the main driver of prostate cancer (PCa). Truncated isoforms of the AR called androgen receptor variants (AR-Vs) lacking the ligand binding domain often emerge during treatment resistance against AR pathway inhibitors such as Enzalutamide. This review discusses how AR-Vs drive a more aggressive form of PCa through the regulation of some of their target genes involved in oncogenic pathways, enabling disease progression. There is a pressing need for the development of a new generation of AR inhibitors which can repress the activity of both the full-length AR and AR-Vs, for which the knowledge of differentially expressed target genes will allow evaluation of inhibition efficacy. This review provides a detailed account of the most common variant, AR-V7, the AR-V7 regulated genes which have been experimentally validated, endeavours to understand their relevance in aggressive AR-V driven PCa and discusses the utility of the downstream protein products as potential drug targets for PCa treatment.

show abstract

“…This means that salicylic acid has a low and high potential to cause interactions with other drugs that are a substrate of the CYP2E1 enzyme in the rat liver microsomes. According to our recent publication, salicylic acid uncompetitively inhibited the UGT2B17 enzyme activity in human supersomes [ 18 ]. This implies that salicylic acid has a negligible effect to cause a drug interaction with other UGT2B17 substrate drugs.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of an HPLC-UV Method for the Quantification of 4′-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug–Drug Interaction in Rat Liver Microsomes

Salhab

Barker

2022

Molecules

Self Cite

View full text Add to dashboard Cite

Salicylic acid is a key compound in nonsteroidal anti-inflammatory drugs that has been recently used for preventing the risk of hospitalization and death among COVID-19 patients and in preventing colorectal cancer (CRC) by suppressing two key proteins. Understanding drug–drug interaction pathways prevent the occurrence of adverse drug reactions in clinical trials. Drug–drug interactions can result in the variation of the pharmacodynamics and pharmacokinetic of the drug. Inhibition of the Cytochrome P450 enzyme activity leads to the withdrawal of the drug from the market. The aim of this paper was to develop and validate an HPLC-UV method for the quantification of 4′-hydroxydiclofenac as a CYP2C9 metabolite using salicylic acid as an inhibitor in rat liver microsomes. A CYP2C9 assay was developed and validated on the reversed phase C18 column (SUPELCO 25 cm × 4.6 mm × 5 µm) using a low-pressure gradient elution programming at T = 30 °C, a wavelength of 282 nm, and a flow rate of 1 mL/min. 4′-hydroxydiclofenac demonstrated a good linearity (R2 > 0.99), good reproducibility, low detection, and quantitation limit, and the inter and intra-day precision met the ICH guidelines (<15%). 4′-hydroxydiclofenac was stable for three days and showed an acceptable accuracy and recovery (80–120%) within the ICH guidelines in a rat liver microsome sample. This method will be beneficial for future applications of the in vitro inhibitory effect of salicylic acid on the CYP2C9 enzyme activity in rat microsomes and the in vivo administration of salicylic acid in clinical trials.

show abstract

Potential Assessment of UGT2B17 Inhibition by Salicylic Acid in Human Supersomes In Vitro

Cited by 3 publications

References 17 publications

Untitled

Untitled

A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer

Development and Validation of an HPLC-UV Method for the Quantification of 4′-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug–Drug Interaction in Rat Liver Microsomes

Contact Info

Product

Resources

About