Demethylzeylasteral exhibits strong inhibition towards UDP-glucuronosyltransferase (UGT) 1A6 and 2B7.

Inhibition of UDP-glucuronosyltransferase (UGT) isoforms can result in severe clinical results, including clinical drug-drug interactions (DDI) and metabolic disorders of endogenous substances. The present study aims to investigate the inhibition of demethylzeylasteral (an important active component isolated from Tripterygium wilfordii Hook F.) towards three important UGT isoforms UGT1A6, UGT1A9 and UGT2B7. The results showed that 100 µM of demethylzeylasteral exhibited strong inhibition towards UGT1A6 and UGT2B7, with negligible influence towards UGT1A9. Furthermore, Dixon and Lineweaver-Burk plots showed the inhibition of UGT1A6 and UGT2B7 by demethylzeylasteral was best fit to competitive inhibition, and the inhibition kinetic parameters (Ki) were calculated to be 0.6 µM and 17.3 µM for UGT1A6 and UGT2B7, respectively. This kind of inhibitory effect need much attention when demethylzeylasteral and demethylzeyasteral-containing herbs (e.g., Tripterygium wilfordii Hook F.) were co-administered with the drugs mainly undergoing UGT1A6, UGT2B7-catalyzed metabolism. However, when extrapolating the in vivo clinical results using our present in vitro data, many complex factors might affect final results, including the contribution of UGT1A6 and UGT2B7 to the metabolism of compounds, and the herbal or patients' factors affecting the in vivo concentration of demethylzeylasteral.

Analysis of HYAL3 gene mutations in Chinese lung squamous cell carcinoma patients.

PURPOSE: In a previous study, we found a hyaluronidase 3 (HYAL3) gene mutation in exon 2 at position 188 by genome sequencing in a lung squamous cell carcinoma patient. The mutation results in substitution of serine for alanine. The aim of the study was to screen the HYAL3 gene mutation in Chinese lung squamous cell carcinoma patients and explore the correlation between mutation of HYAL3 with clinical and pathological characteristics in lung squamous cell carcinoma patients in China. METHODS: We applied polymerase chain reaction to examine the HYAL3 gene mutations in cancer tissues and their adjacent normal tissues from 39 cases of lung squamous cell carcinoma patients. RESULTS: 1) The incidence rate of HYAL3 mutation in 39 cases of lung squamous cell carcinoma was 10.26% (4/39) and none in adjacent normal lung tissues (0/39). 2) The mutations of HYAL3 in the 4 cases were all heterozygous: 3 of them were located in exon 1 (G-T) and one in exon 2 (G-T). 3) Mutations of the HYAL3 gene were not correlated with the distribution of patient gender, age, tumor size, histological grade, smoking history, TNM stage or distant metastasis (P >0.05). The gene mutation was correlated with lymph node status (P = 0.044). CONCLUSION: Mutations of the HYAL3 gene are rare in Chinese lung squamous cell carcinoma patients and might contribute to lymph node metastasis.