Consumption of Garlic and Lemon Aqueous Extracts Combination Reduces Tumor Burden by Angiogenesis Inhibition, Apoptosis Induction, and Immune System Modulation

Nutrition. Nov-Dec 2017;43-44:89-97. doi: 10.1016/j.nut.2017.06.015. Epub 2017 Jul 6.

Abstract

Objectives: Dietary agents play an important role in cancer prevention and therapy because of their low toxicity and the perception that they are not a medicine. The aim of the present study was to investigate the anticancer effect of the administration of garlic and lemon aqueous extracts against breast cancer implanted in mice.

Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to determine the antiproliferative effect of both extracts and their combinations. Isobolographic method was used to calculate the combination index. Balb/C mice were inoculated with EMT6/P breast cancer cells and received intragastric administration of one of three treatments (garlic alone, lemon alone, or a combination of both). Change in tumor size and survival rates were measured. TUNEL assay was used to measure apoptosis and enzyme-linked immunosorbent assay (ELISA) was used to measure vascular endothelial growth factor expression. Serum levels of interferon-γ, interleukin (IL)-2, IL-4, and IL-10 were measured using ELISA and levels of aspartate transaminase, alanine transaminase, and creatinine were determined.

Results: The combination of both extracts acts synergistically against breast cancer in mice. Of the treated mice, 80% were cured using this combination. This combination inhibited angiogenesis, induced apoptosis, and caused systemic activation in the immune system.

Conclusions: The combination of garlic and lemon aqueous extracts represents a promising option to develop an anticancer food for augmenting conventional anticancer therapies. However, further testing is essential to understand the exact molecular mechanisms of this combination and to test its therapeutic effect against other cancer models.

Keywords: Angiogenesis inhibition; Anticancer functional food; Apoptosis induction; Breast cancer; Combination therapy.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Citrus*
  • Drug Synergism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fruit / chemistry
  • Garlic / chemistry*
  • Immunity / drug effects*
  • Interferon-gamma / blood
  • Interleukins / blood
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / prevention & control*
  • Phytotherapy
  • Plant Extracts / administration & dosage*
  • Plant Tubers / chemistry
  • Tumor Burden / drug effects

Substances

  • Anticarcinogenic Agents
  • Interleukins
  • Plant Extracts
  • Interferon-gamma