Antitumoral Potential of Artepillin C, a Compound Derived from Brazilian Propolis, against Breast Cancer Cell Lines

Anticancer Agents Med Chem. 2024;24(2):117-124. doi: 10.2174/0118715206270534231103074433.

Abstract

Background: Breast cancer is the most commonly diagnosed cancer among women worldwide with limited treatment options. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is one of the main constituents of Brazilian propolis presenting different activities, including antitumoral effects against various types of cancer.

Objective: We evaluated the antitumoral potential and mechanisms of action of artepillin C against two distinct human breast cancer cell lines, MCF-7 and MDA-MB-231, to explore a new therapeutic candidate.

Methods: Cell viability was assessed by MTT assay and the long-term cytotoxicity was performed by clonogenic assay. The morphological changes were observed by light microscopy, analysis of cell death pathway by Annexin V FITC/propidium iodide (PI), lactate dehydrogenase (LDH) by colorimetry, DNA fragmentation by agarose gel and senescence by β-galactosidase. Detection of total reactive oxygen species (ROS) by fluorescence microscopy and determination of mitochondrial transmembrane potential by flow cytometry were also performed.

Results: Artepillin C presented a strong and dose-time-dependent cytotoxic effect on MCF-7 and MDA-MB-231 cell lines, with cytotoxicity more evident in MCF-7. In both cancer cell lines, the clonogenic potential was significantly reduced and the morphology of the cells was changed. The treatment also induced death by necrosis and late apoptosis in MCF-7 and MDA-MB-231 and induced cell senescence in MCF-7. Also, artepillin C increased total ROS in both cancer cells and decreased mitochondrial membrane potential in MDA-MB-231 cells.

Conclusion: Artepillin C presented antitumoral potential in two human breast cancer cell lines, MCF-7, and MDA-MB-231, suggesting a new promising option for the treatment and/or chemopreventive strategy for breast cancer.

Keywords: Artepillin C; antitumor effect.; breast cancer cells; cytotoxicity; natural products; propolis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Brazil
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • MCF-7 Cells
  • Phenylpropionates*
  • Propolis* / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • artepillin C
  • Propolis
  • Reactive Oxygen Species
  • Antineoplastic Agents
  • Phenylpropionates