Apple pectin: A natural source for cancer suppression in 4T1 breast cancer cells in vitro and express p53 in mouse bearing 4T1 cancer tumors, in vivo

Biomed Pharmacother. 2016 Dec;84:637-644. doi: 10.1016/j.biopha.2016.09.080. Epub 2016 Sep 30.

Abstract

Purpose: Increase in the number of cancer related deaths has made the study on developing new drugs and treatments essential. One of the main aims in developing new therapies is to use natural resources which have the ability to induce apoptosis. Pectin is one of these natural compounds, a complex polysaccharide found in apples with anti-cancer properties. The aim of this study was to examine anti-cancer properties of pectic acid both in vitro in 4T1 breast cancer cells and in vivo using an animal model of breast cancer.

Experimental design: MTT cell proliferation assays, double fluorescence staining (acridine orange/ethidium bromide) and cell cycle analysis were employed to measure apoptosis in vitro. 4T1 cells were implanted into female BALB/c mice for in vivo studies. Then tumor volumes, histological analysis and immunohistochemical staining of P53 and tunnel test were applied to evaluate apoptosis in tumors.

Results: The results of in vitro studies showed that concentration of 0.1% of pectic acid could induce apoptosis, inhibit cell growth (p<0.001) and reduce cell attachment, fragmented chromatin, and membrane blebbing as well as blocking the sub-G1 phase (p<0.001). In addition, in vivo studies showed that pectic acid could inhibit the progression of tumors through over-expression of P53 and increasing the number of apoptotic cells.

Conclusion: Our results demonstrated that pectic acid, a natural component of apple, can prevent metastasis in both cancer cell lines and primary tumors. This potential effect is mainly due to its ability to induce apoptosis.

Keywords: 4T1 cells; Apoptosis; Apple pectin; BALB/c mice; Breast cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Adhesion / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chromatin Assembly and Disassembly / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Fruit
  • Malus* / chemistry
  • Mice, Inbred BALB C
  • Pectins / isolation & purification
  • Pectins / pharmacology*
  • Phytotherapy
  • Plants, Medicinal
  • Time Factors
  • Tumor Burden / drug effects
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation

Substances

  • Antineoplastic Agents, Phytogenic
  • Tumor Suppressor Protein p53
  • Pectins
  • polygalacturonic acid