Entry #: 48
Date: 28 April 2018
Section: Phenolic compounds
Topic: Oleuropein and autophagy
Type: Original paper

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D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis


Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells


Taek Ji et al

Citation / Year

(1) / 2018


Oleuropein, mesenchymal stem cells, adipose-derived stem cells, oxidative stress, hydrogen peroxide, autophagic cell death


Cellular-based therapies using stem cells, are already used clinically for certain conditions, and hold great promise for alleviating many diseases. For example, they will have great importance in cases where limited intrinsic regeneration occurs following injury; in this context vascular ischemic conditions are particularly important. In this study, mesenchymal stem cells, which represent multipotent progenitors which undergo asymmetrical division forming a copy of themselves (self-renewal), and cells with the ability to differentiate into various cell types including, osteocytes (bone), chondrocytes (connective tissue), adipocytes (fat), myocytes (muscles), and epithelial (outer surface lining cells), cells (2-4). One the limitations to the utility of cellular therapies is oxidative stress-induced cell-death, apoptosis, and decrease in proliferation (5). Oxidative stress can be caused by exogenous agents and endogenous metabolism, and is problematic when oxidizing effects, reactive oxygen species, and free radical damage exceeds the cellular antioxidant capability (6, 7). Therefore, protection of stem cells from oxidative stress, prior to transplantation may provide an increased therapeutic utility for these cells. In this study, the effects of a major olive-phenolic, oleuropein was utilised. Oleuropein, an olive secoiridoid, is well-known to possess potent antioxidant effects in vitro and in vivo (8), and therefore the authors hypothesised that it may offer cytoprotective effects in the context of stem cell therapy.

Key points and implications

A conventional cell culture system approach was utilised for this study. Briefly, adipose-derived mesenchymal stem cells, were primed (pre-treated) with oleuropein prior to induction of oxidative stress using hydrogen peroxide. Following the optimisation of concentrations using a classical cell viability assays cells were treated with 100 μM oleuropein (24 hours), followed by treatment with 600 μM hydrogen peroxide (1 hour). Cells were the assayed for evidence of cell-death and apoptosis (annexin V-propidium iodide staining, tunel assay, and analysis of molecular markers including Bax, Bcl-2, and Mcl-1). Autophagic cell death, which is characterised by sequestration of cytoplasmic components into double-membrane autophagosomes for lysosomal degradation (9, 10), was also examined (mTOR, ULK1, Beclin-1, AMPK, and LC3). Overall, the findings indicated that cells primed with oleuropein prior to induction of hydrogen peroxide-induced oxidative stress, were protected from loss of viability, apoptosis, and autophagic cell-death. These findings are very important, and point towards an extension of these experiments to cases where there protected cells are transplanted in vivo, in appropriate models of disease. Potentially enhancing the therapeutic efficacy of cellular-based therapies by antioxidant priming represents an exciting area for further research.

Related publications

  1. S. T. Ji et al., Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells. Biochemical and biophysical research communications 499, 675-680 (2018).
  2. M. F. Pittenger et al., Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147 (1999).
  3. I. Ullah, R. B. Subbarao, G. J. Rho, Human mesenchymal stem cells – current trends and future prospective. Bioscience reports 35, (2015).
  4. M. F. Pittenger, B. J. Martin, Mesenchymal stem cells and their potential as cardiac therapeutics. Circulation research 95, 9-20 (2004).
  5. S. W. Ryter et al., Mechanisms of cell death in oxidative stress. Antioxidants & redox signaling 9, 49-89 (2007).
  6. L. H. Wu et al., Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells. Apoptosis : an international journal on programmed cell death 19, 1654-1663 (2014).
  7. E. Birben, U. M. Sahiner, C. Sackesen, S. Erzurum, O. Kalayci, Oxidative stress and antioxidant defense. The World Allergy Organization journal 5, 9-19 (2012).
  8. S. H. Omar, Oleuropein in olive and its pharmacological effects. Scientia pharmaceutica 78, 133-154 (2010).
  9. J. H. Ha, H. S. Noh, I. W. Shin, J. R. Hahm, D. R. Kim, Mitigation of H2O2-induced autophagic cell death by propofol in H9c2 cardiomyocytes. Cell biology and toxicology 28, 19-29 (2012).
  10. L. Yu et al., Autophagic programmed cell death by selective catalase degradation. Proceedings of the National Academy of Sciences of the United States of America 103, 4952-4957 (2006).