Flax seed oil reduced tumor growth, modulated immune responses and decreased HPV E6 and E7 oncoprotein expression in a murine model of ectopic cervical cancer

Prostaglandins Other Lipid Mediat. 2019 Aug:143:106332. doi: 10.1016/j.prostaglandins.2019.04.002. Epub 2019 Apr 6.

Abstract

Cervical cancer is the second leading cause of cancer death in women in India. Previously, we have reported that alpha linolenic acid (ALA), induced apoptosis in cervical cancer cell lines and reduced expression of E6 and E7 oncoproteins with simultaneous decrease in Cox2/VEGF/MAP kinase proteins. Here, we investigated the tumor retardation potential of flax oil (FO), rich in ALA, in mouse papilloma model. Flax oil significantly reduced tumor volume and weight in mice compared to the Tumor control (TC) group. Interestingly, compared to cisplatin (Cis) alone, there was slightly enhanced decrease in tumor weight when FO was given together with Cis (Cis + FO). A marked increase in plasma antioxidant levels in mice, and increase in lipid peroxidation in tumors with simultaneous decrease in liver tissues was observed in Cis + FO group compared to either TC or Cis groups. FO and Cis + FO significantly modulated immune response in mice by increasing CD8α and IFNγ and decreasing IL-4 expression. Interestingly, when given together with cisplatin, flax oil reduced HPV E6 and E7 oncoprotein expression with concomitant increase in the relative mRNA expression of tumor suppressor genes p53 and Rb. Thus, flax oil could be explored for its therapeutic potential in cervical cancer.

Keywords: Cervical cancer; Flax oil; Lipid peroxidation; Papilloma model; Th1/Th2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • CD8 Antigens / metabolism
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Fatty Acids / analysis
  • Fatty Acids / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • HeLa Cells
  • Humans
  • Immunomodulation / drug effects*
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Linseed Oil / chemistry
  • Linseed Oil / pharmacology*
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Mice
  • Oncogene Proteins, Viral / metabolism*
  • Papillomavirus E7 Proteins / metabolism*
  • Repressor Proteins / metabolism*
  • Retinoblastoma Protein / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Uterine Cervical Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Antioxidants
  • CD8 Antigens
  • CD8alpha antigen
  • E6 protein, Human papillomavirus type 16
  • Fatty Acids
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • oncogene protein E7, Human papillomavirus type 16
  • Interleukin-4
  • Linseed Oil
  • Interferon-gamma