Anti-Estrogenic and Anti-Cell Proliferative Effect of Allyl Isothiocyanate in Chemoprevention of Chemically Induced Mammary Carcinogenesis in Rats

Pathol Oncol Res. 2020 Apr;26(2):913-925. doi: 10.1007/s12253-019-00638-9. Epub 2019 Mar 20.

Abstract

The anti-estrogenic and anti-cell proliferative effect of allyl isothiocyanate (AITC) was carried out by analyzing the status of sex hormones and its receptors and cell proliferative markers in chemically induced mammary carcinogenesis in rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) and MNU (50 mg/kg bw) injected subcutaneously near mammary gland. RT-PCR, western blotting and immunohistochemical analysis of mammary tissues show an upregulation of ER-α, PR, aromatase, PCNA, cyclin D1 and AgNORs staining and down regulation of p53 expression as well as plasma estradiol, prolactin and testosterone levels increased in DMBA and MNU-induced tumor bearing rats. Oral administration of AITC at a dose of 20 mg/kg bw restored the levels of sex hormones and its receptors, aromatase, cell proliferative markers and AgNORs staining near to normal levels. Molecular docking studies also supported these findings. The results suggest that anti-estrogenic and anti-proliferative effect of AITC prevent the development of DMBA and MNU-induced mammary carcinogenesis in rat.

Keywords: 7,12-dimethylbenz(a)anthracene; Allyl isothiocyanatep; Cell proliferation; Chemoprevention; Mammary carcinogenesis; N-methyl-N-nitrosourea.

MeSH terms

  • Animals
  • Anthracenes / toxicity
  • Carcinogens / toxicity
  • Cell Proliferation / drug effects*
  • Chemoprevention / methods
  • Estrogen Receptor Modulators / pharmacology*
  • Female
  • Isothiocyanates / pharmacology*
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / pathology*
  • Methylnitrosourea / toxicity
  • Piperidines / toxicity
  • Rats
  • Rats, Sprague-Dawley

Substances

  • 3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene
  • Anthracenes
  • Carcinogens
  • Estrogen Receptor Modulators
  • Isothiocyanates
  • Piperidines
  • Methylnitrosourea
  • allyl isothiocyanate