Eugenol inhibits non‐small cell lung cancer by repressing expression of NF‐κB‐regulated TRIM59

Abstract

In view of the recognized anti‐tumor properties of eugenol against non‐small cell lung cancer (NSCLC) in cell culture, here we further set out to investigate the potential therapeutic effect of eugenol in vivo and elucidate the underlying molecular mechanism. The relative expression levels of TRIM59 and p65 in NSCLC were quantified by real‐time polymerase chain reaction. Xenograft tumor model was established with TRIM59‐deficient H1975 cells, and tumor progression was monitored. Kaplan–Meier's analysis was performed to measure overall survival. Protein levels of TRIM59 and p65 in xenograft tumor were determined by western blot. Direct binding of p65 on the TRIM59 promoter was analyzed by chromatin immunoprecipitation assay, and the regulatory effect was interrogated with luciferase reporter assay. Both TRIM59 and p65 were up‐regulated in NSCLC. Eugenol treatment significantly inhibited xenograft tumor progression and prolonged the overall survival of tumor‐bearing mice. Mechanistically, eugenol suppressed p65 expression, which subsequently decreased TRIM59 expression. TRIM59 deficiency fully recapitulated the anti‐tumoral phenotype elicited by eugenol. Ectopic expression of TRIM59 completely abolished the tumor suppressive effect of eugenol, which underlined the predominant role of TRIM59 in mediating the signaling downstream of eugenol treatment. Eugenol inhibited NSCLC via repression NF‐κB‐TRIM59 pathway.

TRIM59 loss in M2 macrophages promotes melanoma migration and invasion by upregulating MMP-9 and Madcam1

“…TRIM59, a member of the TRIM ubiquitin ligase family, has long been considered a tumor marker in association with tumor progression and metastasis in several tumor types, such as non-small cell lung cancer, gastric cancer, osteosarcoma, and cervical cancer [17, 43–46]. A recent study reported that depletion of TRIM59 suppresses breast cancer metastasis by promoting RNFT1-induced K63 poly ubiquitination and SQSTM1-directed autophagic degradation of PDCD10 [40].…”

The protective effect and potential mechanisms of eugenol against Salmonella in vivo and in vitro

“…Clove oil is a clear pale yellowish volatile liquid extracted from Syzygium aromaticum , Myrtaceae, and it is widely used in ambulatory anaesthetization ( Correia et al., 2018 ). Eugenol (C 10 H 12 O 2 ; 2-methoxy-4-2-propenyl), the principal active ingredient in clove oil, is well-known for its antibacterial, antifungal, anti-inflammatory, neuroprotective, and antineoplastic properties ( Cui et al., 2019 ; Garabadu and Sharma, 2019 ; Oroojan, 2020 ; Sakat et al., 2019 ; Tandel et al., 2021 ). In light of that eugenol has acquired a “Generally Recognized as Safe” status from the US Food and Drug Administration, it has extensive applications in pharmaceutical application, health care and cosmetology ( Nisar et al., 2021 ).…”

Global regulatory factor FsveA up-regulate the production of antitumor substance in endophytic Fusarium solani

“…Cinnamaldehyde inhibits proliferation, migration, invasion and promotes apoptosis of OS cells and is a potentially valid antitumor agent (Huang et al 2020). 4-Allyl-2-methoxyphenol inhibits non-small cell lung cancer by inhibiting NF-B to regulate TRIM59 expression (Cui et al 2019). Epicatechin gallate can be combined with other compounds to form novel agents that inhibit the tumorigenicity of human papillomavirus-positive head and neck squamous cell carcinomas (Piao et al 2016).…”