In Vitro and In Vivo Anticancer Activity of the Most Cytotoxic Fraction of Pistachio Hull Extract in Breast Cancer

Molecules. 2020 Apr 13;25(8):1776. doi: 10.3390/molecules25081776.

Abstract

Pistacia (Pistacia vera) hulls (PV) is a health product that has been determined to contain bioactive phytochemicals which have fundamental importance for biomedical use. In this study, PV ethyl acetate extraction (PV-EA) fractions were evaluated with the use of an MTT assay to find the most cytotoxic fraction, which was found to be F13b1/PV-EA. After that, HPTLC was used for identify the most active compounds. The antioxidant activity was analyzed with DPPH and ABTS tests. Apoptosis induction in MCF-7 cells by F13b1/PV-EA was validated via flow cytometry analysis and a distinctive nuclear staining method. The representation of genes like Caspase 3, Caspase 8, Bax, Bcl-2, CAT and SOD was assessed via a reverse transcription (RT_PCR) method. Inhabitation of Tubo breast cancer cell development was examined in the BALB-neuT mouse with histopathology observations. The most abundant active components available in our extract were gallic acid and the flavonoid quercetin. The F13b1/PV-EA has antiradical activity evidence by its inhibition of ABTS and DPPH free radicals. F13b1/PV-EA displayed against MCF-7 a suppressive effect with an IC50 value of 15.2 ± 1.35 µg/mL. Also, the expression of CAT, SOD, Caspase 3, Caspase 8 and Bax increased and the expression of Bcl-2 decreased. F13b1/PV-EA dose-dependently inhibited tumor development in cancer-induced mice. Thus, this finding introduces F13b1/PV-EA as an effectual apoptosis and antitumor active agent against breast cancer.

Keywords: anticancer; breast cancer; pistacia (Pistacia vera) hulls.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antineoplastic Agents, Phytogenic / toxicity
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Antioxidants / toxicity
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Caspases / genetics
  • Caspases / metabolism
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Chromatography, Thin Layer
  • Gallic Acid / analysis
  • Gallic Acid / pharmacology
  • Gallic Acid / therapeutic use
  • Humans
  • Inhibitory Concentration 50
  • Lethal Dose 50
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pistacia / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Plant Extracts / toxicity
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Quercetin / analysis
  • Quercetin / pharmacology
  • Quercetin / therapeutic use
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism
  • Transplantation, Homologous
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Gallic Acid
  • Quercetin
  • Catalase
  • Superoxide Dismutase-1
  • Caspases