In Vivo Chemosuppressive Effects of Kolaviron on 7,12-Dimethylbenzanthracene-Induced Mammary Lesions are Associated with Changes in Levels of Estrogen Receptor-α, CYP 1A1, Proinflammatory Cytokines, and Alterations to Metabolic Pathways Implicated in Mammary Carcinogenesis

J Med Food. 2024 Oct;27(10):940-950. doi: 10.1089/jmf.2023.0158. Epub 2024 Aug 2.

Abstract

Garcinia kola is a medicinal food commonly consumed in Sub-Sahara Africa, for which Kolaviron (KV) is the active portion. As a follow-up to our earlier chemopreventive studies, we investigated the chemotherapeutic effects of KV on experimentally induced mammary carcinogenesis in female Wistar rats. Mammary carcinogenesis was induced using 80 mg/kg of 7,12-dimethylbenzanthracene (DMBA) administered by oral gavage. One hundred-fifty days post-DMBA induction, estrogen receptor-α (ER-α) levels were determined in the experimental rats before treatment with KV commenced. Treatment was done using 50, 100, and 200 mg/kg KV thrice a week for 4 weeks, after which the experiment was terminated. Significantly higher levels of estrogen receptor-α, CYP 1A1, malondialdehyde, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased cytokine (interleukin-6 and tumor necrosis factor-α) activity were observed in DMBA-induced rats, which were attenuated in KV-treated rats. Tyrosine metabolism was exclusively enriched in DMBA-induced rats in contrast to KV-treated rats. Collectively, the results point to the chemotherapeutic potential of KV.

Keywords: Garcinia kola; biotherapeutics; carcinogenesis; kolaviron; mammary damage.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene* / toxicity
  • Animals
  • Carcinogenesis / chemically induced
  • Carcinogenesis / drug effects
  • Cytochrome P-450 CYP1A1* / genetics
  • Cytochrome P-450 CYP1A1* / metabolism
  • Cytokines / metabolism
  • Estrogen Receptor alpha* / genetics
  • Estrogen Receptor alpha* / metabolism
  • Female
  • Flavonoids* / pharmacology
  • Garcinia kola / chemistry
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / metabolism
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Wistar*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 9,10-Dimethyl-1,2-benzanthracene
  • Estrogen Receptor alpha
  • kolaviron
  • Cytochrome P-450 CYP1A1
  • Flavonoids
  • Cytokines
  • Plant Extracts
  • Interleukin-6
  • Tumor Necrosis Factor-alpha