Bestatin Cream Impairs Solar Simulated Light‒Driven Skin Inflammation and Skin Carcinogenesis in Mice

Simin Zhao, Ke Yao, Kangdong Liu, Limeng Huang, Yanan Jiang, Jian Li, Ziming Dong, Zigang Dong

Research output: Contribution to journalArticlepeer-review

Abstract

Leukotriene A4 hydrolase (LTA4H) is an enzyme that catalyzes the production of the inflammatory mediator leukotriene B4, which is involved in inflammatory responses mediated through the leukotriene B4/leukotriene B4 receptor type 1 (BLT1) signaling pathway. In this study, we investigated whether bestatin, an LTA4H inhibitor, could suppress skin acute inflammation and carcinogenesis. In the clinical sample, BLT1 was significantly induced in human skin tissues after acute solar simulated light (SSL) exposure. BLT1 and NF-κB p65 expressions were also increased in acute SSL‒induced mouse skin tissue. Furthermore, LTA4H and BLT1 were highly expressed in skin chronic inflammation and squamous cell carcinomas. More importantly, topical administration of bestatin cream dramatically inhibited BLT1 expression in acute SSL‒induced human skin tissues. BLT1 and NF-κB p65 expressions were also suppressed in acute SSL‒induced Lta4h-knockout and bestatin-treated mice skin tissues. Moreover, we conducted long-term prevention and therapeutic studies, which showed that bestatin significantly attenuated SSL-induced skin carcinogenesis. Mechanistic studies showed that bestatin inhibited skin carcinogenesis by suppressing cell proliferation and inducing cell apoptosis through LTA4H‒BLT1‒protein kinase B‒NF-κB p65 pathway. Overall, our results suggest that topical application of novel cream containing bestatin might open a helpful avenue for SSL-induced skin carcinogenesis.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
Early online dateMay 26 2021
DOIs
StateE-pub ahead of print - May 26 2021

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China , Beijing, China (numbers 81472324 and 81572812 ) and the Henan Province Science and Technology Project (number 212102310880 ). The authors thank Tianshun Zhang and Qiushi Wang, University of Minnesota, Austin, MN, for their help.

Funding Information:
This work was supported by the National Natural Science Foundation of China, Beijing, China (numbers 81472324 and 81572812) and the Henan Province Science and Technology Project (number 212102310880). The authors thank Tianshun Zhang and Qiushi Wang, University of Minnesota, Austin, MN, for their help. Conceptualization: SZ, ZigD; Data Curation: SZ, KY, KL; Investigation: YJ, JL; Writing - Original Draft Preparation: SZ, KY, KL; Writing - Review and Editing: SZ, LH, ZimD

Publisher Copyright:
© 2021 The Authors

PubMed: MeSH publication types

  • Journal Article

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