GLA supplementation regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DMBA induced mammary gland carcinoma

Int J Biochem Cell Biol. 2018 Mar:96:51-62. doi: 10.1016/j.biocel.2018.01.011. Epub 2018 Feb 2.

Abstract

The aim of the present study is to evaluate the effect of gamma linolenic acid (GLA) on mitochondrial mediated death apoptosis, hypoxic microenvironment and cholinergic anti-inflammatory pathway against 7, 12-dimethylbenz (a) anthracene (DMBA) induced mammary gland carcinoma. The effects of GLA were evaluated morphologically and biochemically against DMBA induced mammary gland carcinoma. The metabolic study was done for evaluation of biomarkers using 1H NMR. The present study was also verified through immunoblotting and qRT-PCR studies for the evaluation of various pathways. GLA treatment has a delineate implementation upon morphology of the tissues when evaluated through carmine staining, hematoxyline and eosin staining and scanning electron microscopy. GLA also demarked a commendatory proclamation of the fifteen key serum metabolites analogous with amino acid metabolism and fatty acid metabolism when recognized through1H NMR studies. The immunoblotting and qRT-PCR studies accomplished that GLA mediated mitochondrial death apoptosis, curtail hypoxic microenvironment along with hindrance of de novo fatty acid synthesis and also mediate the cholinergic anti-inflammatory pathway to proclaim its anticancer effects.

Keywords: 7, 12-Dimethylbenz (a) anthracene; Breast cancer; Gamma linolenic acid; Hypoxia; Mitochondria mediated death apoptosis; alpha-7-nachr.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthracenes / toxicity*
  • Apoptosis / drug effects*
  • Female
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Neoplasm Proteins / metabolism*
  • Piperidines / toxicity*
  • Procollagen-Proline Dioxygenase / metabolism*
  • Rats
  • Rats, Wistar
  • Tumor Hypoxia / drug effects*
  • gamma-Linolenic Acid / pharmacology*

Substances

  • 3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene
  • Anthracenes
  • Neoplasm Proteins
  • Piperidines
  • gamma-Linolenic Acid
  • Procollagen-Proline Dioxygenase
  • Egln1 protein, rat
  • Hypoxia-Inducible Factor-Proline Dioxygenases