Zingerone induced caspase-dependent apoptosis in MCF-7 cells and prevents 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in experimental rats

J Biochem Mol Toxicol. 2019 Oct;33(10):e22387. doi: 10.1002/jbt.22387. Epub 2019 Sep 2.

Abstract

Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12-dimethylbenz(a)anthracene (DMBA)-treated mammary carcinogenesis in Sprague-Dawley (SD) rats and MCF-7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA-induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt-b5 and CYP450 ) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl-2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA-induced mammary cancer in SD animals and Michigan cancer foundation-7 mammary cancer cells.

Keywords: 7,12-dimethylbenz(a)anthracene; MCF-7 cell lines; anticancer; antioxidant; reactive oxygen species; zingerone.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Apoptosis / drug effects*
  • Biotransformation
  • Blotting, Western
  • Carcinogens / pharmacology*
  • Caspases / metabolism*
  • Guaiacol / analogs & derivatives*
  • Guaiacol / pharmacology
  • Humans
  • Lipid Peroxidation / drug effects
  • MCF-7 Cells
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • Carcinogens
  • Reactive Oxygen Species
  • zingerone
  • 9,10-Dimethyl-1,2-benzanthracene
  • Guaiacol
  • Caspases