Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells

Abstract

Apigenin is found in several dietary plant foods such as vegetables and fruits. To investigate potential anticancer properties of apigenin on human breast cancer, ER-positive MCF-7 and triple-negative MDA MB-231 cells were used. Moreover, toxicological safety of apigenin towards normal cells was evaluated in human lymphocytes. Cytotoxicity of apigenin towards cancer cells was evaluated by MTT assay whereas further genotoxic and oxidative stress parameters were measured by comet and lipid peroxidation assays, respectively. In order to examine the type of cell death induced by apigenin, several biomarkers were used. Toxicological safety towards normal cells was evaluated by cell viability and comet assays. After the treatment with apigenin, we observed changes in cell morphology in a dose- (10 to 100 μM) and time-dependent manner. Moreover, apigenin caused cell death in both cell lines leading to significant toxicity and dominantly to apoptosis. Furthermore, apigenin proved to be genotoxic towards the selected cancer cells with a potential to induce oxidative damage to lipids. Of great importance is that no significant cytogenotoxic effects were detected in normal cells. The observed cytogenotoxic and pro-cell death activities of apigenin coupled with its low toxicity towards normal cells indicate that this natural product could be used as a future anticancer modality. Therefore, further analysis to determine the exact mechanism of action and in vivo studies on animal models are warranted.

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Acknowledgments

This work was supported by the funds and equipment from the University of Zagreb, Faculty of Science and Faculty of Pharmacy and Biochemistry, Ruđer Bošković Institute, and the Institute for Medical Research and Occupational Health. The authors would like to thank Prof. Dr. Ana-Marija Domijan for HPLC analysis support, Prof. Dr. Maja Matulić for providing necessary cells and chemicals, and Ms. Željana Pavlaković for manuscript language editing.

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Correspondence to Goran Gajski.

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The study was approved by the Institutional Ethics committee and observed the ethical principles of the Declaration of Helsinki.

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Vrhovac Madunić, I., Madunić, J., Antunović, M. et al. Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn-Schmiedeberg's Arch Pharmacol 391, 537–550 (2018). https://doi.org/10.1007/s00210-018-1486-4

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Keywords

  • Apigenin
  • Breast cancer cells
  • Human lymphocytes
  • Cytogenotoxicity
  • Apoptosis
  • Anticancer effect