The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action

Apoptosis. 2023 Aug;28(7-8):1184-1197. doi: 10.1007/s10495-023-01852-2. Epub 2023 May 13.

Abstract

This study was designed to assess the ameliorative effects of eugenol and to propose the possible mechanisms of action of eugenol in diethylnitrosamine (DENA)/acetylaminofluorene (AAF)-caused lung cancer in Wistar rats. To induce lung cancer, DENA at a dose of 150 mg/kg body weight (b.wt) for 2 weeks were intraperitoneally injected once each week and AAF was administered orally at a dose of 20 mg/kg b.wt. four times each week for the next 3 weeks. DENA/AAF-administered rats were orally supplemented with eugenol at a dose of 20 mg/kg b.wt administered once a day until 17 weeks starting from the 1st week of DENA administration. Lung histological lesions, including sheets of tumor cells, micropapillary adenocarcinoma, and apoptotic cells, resulting from the DENA/AAF dosage, were ameliorated by eugenol treatment. However, a significant drop in the levels of LPO in the lungs and a remarkable rise in GSH content and GPx and SOD activities were observed in DENA/AAF-administered rats treated with eugenol compared with those in DENA/AAF-administered controls. Moreover, in DENA/AAF-administered rats, eugenol supplementation significantly reduced TNF-α and IL-1β levels and mRNA expression levels of NF-κB, NF-κB p65, and MCP-1 but significantly elevated the level of Nrf2. Furthermore, the DENA/AAF-administered rats treated with eugenol exhibited a significant downregulation of Bcl-2 expression levels in addition to a significant upregulation in P53 and Bax expression levels. Otherwise, the administration of DENA/AAF elevated the protein expression level of Ki-67, and this elevation was reversed by eugenol treatment. In conclusion, eugenol has effective antioxidant, anti-inflammatory, proapoptotic, and antiproliferative properties against lung cancer.

Keywords: Acetylaminofluorene; Apoptosis; Diethylnitrosamine; Eugenol; Inflammation; Lung cancer.

MeSH terms

  • 2-Acetylaminofluorene / adverse effects
  • 2-Acetylaminofluorene / metabolism
  • Animals
  • Anticarcinogenic Agents* / pharmacology
  • Anticarcinogenic Agents* / therapeutic use
  • Apoptosis
  • Diethylnitrosamine / metabolism
  • Diethylnitrosamine / toxicity
  • Eugenol / adverse effects
  • Liver / pathology
  • Liver Neoplasms, Experimental* / chemically induced
  • Liver Neoplasms, Experimental* / metabolism
  • Liver Neoplasms, Experimental* / pathology
  • Lung Neoplasms* / chemically induced
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Anticarcinogenic Agents
  • 2-Acetylaminofluorene
  • Diethylnitrosamine
  • Eugenol
  • NF-kappa B