Study on antitumor, antioxidant and immunoregulatory activities of the purified polyphenols from pinecone of Pinus koraiensis on tumor-bearing S180 mice in vivo

Int J Biol Macromol. 2017 Jan;94(Pt A):735-744. doi: 10.1016/j.ijbiomac.2016.10.071. Epub 2016 Oct 26.

Abstract

Pinecone polyphenols are bioactive dietary constituents that enhance health and help prevent and treat cancer through improving antioxidant and immunoregulatory activities. This study was designed to investigate the antitumor, antioxidant and immunoregulatory activities of the 40% ethanol eluent of polyphenols from pinecone of pinus koraiensis (PPP-40) in Sarcoma 180 (S180)-bearing mice models in vivo. The results of antitumor activity indicated that PPP-40 significantly inhibited S180 tumor growth and the dose of 150mg/kg exhibited the highest antitumor activity. Moreover, TdT-mediated dUTP nick end labeling (TUNEL) assay results further confirmed the apoptosis of S180 tumor cells. In addition, PPP-40 could obviously promote the expressions of Bax protein and inhibit the Bcl-2 protein, accordingly improve the expressions of activated Caspase-3 as well, which resulted in the activation of mitochondrial apoptotic pathway of tumor cells in S180 mice eventually. The results of antioxidant activity showed that the S180 mice treated with PPP-40 had the higher superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, the more glutathione (GSH) content, and the lower malondialdehyde (MDA) level in plasma comparing with non-treated control group. Moreover, the administration with PPP-40 (150mg/kg) significantly accelerated the proliferation of splenocytes (p<0.01) and increased the monocyte phagocytosis activity in vivo simultaneously. These results revealed that PPP-40 exerts an effective antitumor activity by activating the mitochondrial apoptotic pathway and improving the antioxidant and immunoregulatory activities.

Keywords: Antioxidant activity; Antitumor activity; Immunoregulatory activity; Pinecone polyphenols; Pinus koraiensis.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / immunology
  • Cell Proliferation / drug effects
  • Cyclophosphamide / pharmacology
  • Gene Expression
  • Glutathione / blood
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / pharmacology*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Male
  • Malondialdehyde / blood
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Transplantation
  • Pinus / chemistry*
  • Polyphenols / isolation & purification
  • Polyphenols / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Sarcoma 180 / blood
  • Sarcoma 180 / drug therapy*
  • Sarcoma 180 / genetics
  • Sarcoma 180 / pathology
  • Spleen / drug effects
  • Spleen / immunology
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / genetics
  • Tumor Burden / drug effects
  • bcl-2-Associated X Protein / agonists
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / immunology

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Bax protein, mouse
  • Immunologic Factors
  • Polyphenols
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Bcl2 protein, mouse
  • Malondialdehyde
  • Cyclophosphamide
  • Superoxide Dismutase
  • Casp3 protein, mouse
  • Caspase 3
  • Glutathione