Antiproliferative Activity of Chemically Characterized Propolis from Turkey and Its Mechanisms of Action

Başak Aru1, Etil Güzelmeric2, Aslı Akgül3

  • 1Department of Immunology, Faculty of Medicine, Yeditepe University, TR-34755, Kayışdağı, İstanbul, Turkey.

Insights

This study shows that Turkish propolis extract has moderate antiproliferative and apoptotic effects on cancer cells, inducing cell cycle arrest. It also uniquely impacts programmed death-ligand 1 (PD-L1) expression in cancer.

Area of Science:

  • Natural Products Chemistry
  • Cancer Biology
  • Immunology

Background:

  • Propolis, a natural resinous mixture produced by honeybees, possesses diverse biological activities.
  • Cancer remains a leading cause of mortality, necessitating novel therapeutic strategies.
  • Immune checkpoint proteins, like PD-L1, are crucial targets in cancer immunotherapy.

Purpose of the Study:

  • To investigate the antiproliferative, apoptotic, and cell cycle effects of Turkish propolis extract on human cancer cell lines (MCF7, HGC27, A549) and a healthy cell line (HUVEC).
  • To analyze the impact of propolis extract on cell cycle proteins (p21, p53, Cyclin D1) and the immune checkpoint protein PD-L1.
  • To identify key chemical constituents of the propolis extract using HPTLC and HPLC.

Main Methods:

  • MTS assay for antiproliferative activity assessment.
  • Flow cytometry and fluorescent imaging for cell cycle analysis and morphological changes.
  • Western blotting to evaluate cell cycle checkpoint proteins (p21, p53, Cyclin D1) and PD-L1 expression.
  • High-Performance Thin-Layer Chromatography (HPTLC) and High-Performance Liquid Chromatography (HPLC) for chemical composition analysis.

Main Results:

  • Propolis extract exhibited moderate antiproliferative effects (IC50: 58.6-90.7 μg/mL) against tested cancer cell lines.
  • The extract induced apoptosis and G0/G1 cell cycle arrest, associated with p21 activation.
  • Significant changes in cell size were observed, and notably, propolis influenced PD-L1 expression on cancer cells, a novel finding.

Conclusions:

  • Ethanolic propolis extract from Northern Turkey demonstrates significant anticancer potential through antiproliferative and apoptotic mechanisms.
  • The extract modulates cell cycle progression and impacts the expression of PD-L1, suggesting a role in immune modulation within the tumor microenvironment.
  • This study highlights propolis as a promising source for developing novel cancer therapeutics and provides the first evidence of its effect on PD-L1 expression.

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