Genistin modulates high-mobility group box protein 1 (HMGB1) and nuclear factor kappa-B (NF-κB) in Ehrlich-ascites-carcinoma-bearing mice

Environ Sci Pollut Res Int. 2023 Jan;30(1):966-978. doi: 10.1007/s11356-022-22268-6. Epub 2022 Jul 30.

Abstract

Cancer is the world's second-largest cause of death. Although there are numerous cancer treatment options, they are typically uncomfortable owing to side effects and ineffectual due to increased resistance to traditional anti-cancer medications or radiation therapy. A key method in cancer treatment is to target delayed/inhibited inflammation and apoptosis, which are very active areas of research. Natural chemicals originating from plants are of particular interest because of their high bioavailability, safety, few side effects, and, most importantly, cost-effectiveness. Flavonoids have become incredibly common as anti-cancer medications, with promising findings as cytotoxic anti-cancer agents that cause cancer cell death. Isolated compound (genistin) was evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7 and MDA-MB-231). The compound exhibited good cytotoxic activities against both cell lines. In vivo antiproliferative efficacy was also investigated in Ehrlich's ascites carcinoma (EAC). Compared to the control group, genistin revealed a significant decrease in tumor weight, volume, high-mobility group box1 (HMGB1), and nuclear factor-kappa B (NF-κB) contents. On the other hand, B-cell lymphoma 2 (Bcl-2) contents increase suggesting an anti-inflammatory and anti-apoptotic activity through inhibition of HMGB1 signaling and activating the Bcl-2 pathway.

Keywords: Bcl-2; Cancer; Ehrlich’s ascites carcinoma; Flavonoids; Genistin; HMGB1; NF-κB.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Ascites / drug therapy
  • Carcinoma, Ehrlich Tumor* / pathology
  • HMGB1 Protein* / metabolism
  • HMGB1 Protein* / pharmacology
  • Humans
  • MCF-7 Cells
  • Mice
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-bcl-2

Substances

  • NF-kappa B
  • genistin
  • HMGB1 Protein
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2