Phytol as an anticarcinogenic and antitumoral agent: An in vivo study in swiss mice with DMBA-Induced breast cancer

IUBMB Life. 2019 Feb;71(2):200-212. doi: 10.1002/iub.1952. Epub 2018 Nov 5.

Abstract

Phytol (PHY) (3,7,11,15-tetramethylhexadec-2-en-1-ol) exhibits various pharmacological properties including toxicity and cytotoxicity, and exerts antitumor activity. Owing to the urgent need of new pharmaceutical formulations for breast cancer therapy, this study aimed at the evaluation of antitumor activity of PHY in 7,12-dimethylbenzanthracene-cancer-induced animal model. Comet assay was employed to evaluate the cytogenetics, DNA repair, and antigenotoxic activities of PHY in neoplastic (breast) and non-neoplastic rodent cells (bone marrow, lymphocytes, and liver). Additionally, hematological, biochemical, histopathological, and immunohistochemical analyses were carried out in experimental animals. Thirty nonpregnant female mice (n = 5) underwent 7 weeks treatment with 6 mg/kg pro-carcinogen, PHY (4 mg/kg), and cyclophosphamide (25 mg/kg). Induction of cancer was confirmed by histopathology and immunohistochemistry for Ki-67. Results suggest that PHY exhibits low toxicity in comparison with other groups in hematological, biochemical, histopathological, and organ size parameters. Additionally, PHY showed modulatory effects on the pro-carcinogen, and induced genotoxicity and apoptosis in breast cancer cells. Furthermore, it showed a DNA damage repair capacity in mouse lymphocytes. These data indicate that PHY may have the potential as an anticancer candidate in pharmaceutical consumption. © 2018 IUBMB Life, 71(1):200-212, 2019.

Keywords: cancer; phytol; risk assessment; toxicogenetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / administration & dosage
  • 9,10-Dimethyl-1,2-benzanthracene / antagonists & inhibitors
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Comet Assay
  • Cyclophosphamide / pharmacology
  • DNA Damage
  • DNA Repair / drug effects*
  • Drug Administration Schedule
  • Female
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Locomotion / drug effects
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Phytol / pharmacology*

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Mki67 protein, mouse
  • Phytol
  • 9,10-Dimethyl-1,2-benzanthracene
  • Cyclophosphamide