Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Pretreatment with Lycopene Attenuates Oxidative Stress-Induced Apoptosis in Human Mesenchymal Stem Cells

  • Kim, Ji Yong (Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University) ;
  • Lee, Jai-Sung (Department of Animal Science and Technology, Sunchon National University) ;
  • Han, Yong-Seok (Medical Science Research Institute, Soonchunhyang University Seoul Hospital) ;
  • Lee, Jun Hee (Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University) ;
  • Bae, Inhyu (Department of Animal Science and Technology, Sunchon National University) ;
  • Yoon, Yeo Min (Medical Science Research Institute, Soonchunhyang University Seoul Hospital) ;
  • Kwon, Sang Mo (Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University) ;
  • Lee, Sang Hun (Medical Science Research Institute, Soonchunhyang University Seoul Hospital)
  • Received : 2015.06.25
  • Accepted : 2015.08.03
  • Published : 2015.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although $H_2O_2$ ($200{\mu}M$) increased intracellular ROS levels in human MSCs, lycopene ($10{\mu}M$) pretreatment suppressed $H_2O_2$-induced ROS generation and increased survival. $H_2O_2$-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by $H_2O_2$ treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.

Keywords

References

  1. Bar-Am, O., Weinreb, O., Amit, T. and Youdim, M. B. (2005) Regulation of Bcl-2 family proteins, neurotrophic factors, and APP processing in the neurorescue activity of propargylamine. FASEB J. 19, 1899-1901. https://doi.org/10.1096/fj.05-3794fje
  2. Bhang, S. H., Cho, S. W., La, W. G., Lee, T. J., Yang, H. S., Sun, A. Y., Baek, S. H., Rhie, J. W. and Kim, B. S. (2011) Angiogenesis in ischemic tissue produced by spheroid grafting of human adiposederived stromal cells. Biomaterials 32, 2734-2747. https://doi.org/10.1016/j.biomaterials.2010.12.035
  3. Castro-Manrreza, M. E. and Montesinos, J. J. (2015) Immunoregulation by mesenchymal stem cells: biological aspects and clinical applications. J. Immunol. Res. 2015, 394917.
  4. Chao, H. H., Sung, L. C., Chen, C. H., Liu, J. C., Chen, J. J. and Cheng, T. H. (2014) Lycopene Inhibits Urotensin-II-Induced Cardiomyocyte Hypertrophy in Neonatal Rat Cardiomyocytes. Evid. Based Complement. Alternat. Med. 2014, 724670.
  5. Chen, Y. C., Lin-Shiau, S. Y. and Lin, J. K. (1998) Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J. Cell. Physiol. 177, 324-333. https://doi.org/10.1002/(SICI)1097-4652(199811)177:2<324::AID-JCP14>3.0.CO;2-9
  6. Chung, Y. M., Park, S. H., Tsai, W. B., Wang, S. Y., Ikeda, M. A., Berek, J. S., Chen, D. J. and Hu, M. C. (2012) FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. Nat. Commun. 3, 1000. https://doi.org/10.1038/ncomms2008
  7. Cohen, G. M. (1997) Caspases: the executioners of apoptosis. Biochem. J. 326, 1-16. https://doi.org/10.1042/bj3260001
  8. Di Mascio, P., Kaiser, S. and Sies, H. (1989) Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch. Biochem. Biophys. 274, 532-538. https://doi.org/10.1016/0003-9861(89)90467-0
  9. Engelhard, Y. N., Gazer, B. and Paran, E. (2006) Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, placebo-controlled pilot study. Am. Heart J. 151, 100.
  10. Engelmann, N. J., Clinton, S. K. and Erdman, J. W., Jr. (2011) Nutritional aspects of phytoene and phytofluene, carotenoid precursors to lycopene. Adv. Nutr. 2, 51-61. https://doi.org/10.3945/an.110.000075
  11. Fearon, I. M. and Faux, S. P. (2009) Oxidative stress and cardiovascular disease: novel tools give (free) radical insight. J. Mol. Cell. Cardiol. 47, 372-381. https://doi.org/10.1016/j.yjmcc.2009.05.013
  12. Frey, R. S. and Mulder, K. M. (1997) Involvement of extracellular signal-regulated kinase 2 and stress-activated protein kinase/Jun N-terminal kinase activation by transforming growth factor beta in the negative growth control of breast cancer cells. Cancer Res. 57, 628-633.
  13. Galluzzi, L., Morselli, E., Kepp, O. and Kroemer, G. (2009) Targeting post-mitochondrial effectors of apoptosis for neuroprotection. Biochem. Biophys. Acta 1787, 402-413.
  14. Hare, J. M., Fishman, J. E., Gerstenblith, G., DiFede Velazquez, D. L., Zambrano, J. P., Suncion, V. Y., Tracy, M., Ghersin, E., Johnston, P. V., Brinker, J. A., Breton, E., Davis-Sproul, J., Schulman, I. H., Byrnes, J., Mendizabal, A. M., Lowery, M. H., Rouy, D., Altman, P., Wong Po Foo, C., Ruiz, P., Amador, A., Da Silva, J., McNiece, I. K., Heldman, A. W., George, R. and Lardo, A. (2012) Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308, 2369-2379. https://doi.org/10.1001/jama.2012.25321
  15. Holzapfel, N. P., Holzapfel, B. M., Champ, S., Feldthusen, J., Clements, J. and Hutmacher, D. W. (2013) The potential role of lycopene for the prevention and therapy of prostate cancer: from molecular mechanisms to clinical evidence. Int. J. Mol. Sci. 14, 14620-14646. https://doi.org/10.3390/ijms140714620
  16. Huwiler, A. and Pfeilschifter, J. (1994) Transforming growth factor beta 2 stimulates acute and chronic activation of the mitogen-activated protein kinase cascade in rat renal mesangial cells. FEBS Lett. 354, 255-258. https://doi.org/10.1016/0014-5793(94)01132-X
  17. Janicke, R. U., Sprengart, M. L., Wati, M. R. and Porter, A. G. (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem. 273, 9357-9360. https://doi.org/10.1074/jbc.273.16.9357
  18. Jin, Y., Kato, T., Furu, M., Nasu, A., Kajita, Y., Mitsui, H., Ueda, M., Aoyama, T., Nakayama, T., Nakamura, T. and Toguchida, J. (2010) Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase. Biochem. Biophys. Res. Commun. 391, 1471-1476. https://doi.org/10.1016/j.bbrc.2009.12.096
  19. Karantalis, V., DiFede, D. L., Gerstenblith, G., Pham, S., Symes, J., Zambrano, J. P., Fishman, J., Pattany, P., McNiece, I., Conte, J., Schulman, S., Wu, K., Shah, A., Breton, E., Davis-Sproul, J., Schwarz, R., Feigenbaum, G., Mushtaq, M., Suncion, V. Y., Lardo, A. C., Borrello, I., Mendizabal, A., Karas, T. Z., Byrnes, J., Lowery, M., Heldman, A. W. and Hare, J. M. (2014) Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial. Circ. Res. 114, 1302-1310. https://doi.org/10.1161/CIRCRESAHA.114.303180
  20. Kelkel, M., Schumacher, M., Dicato, M. and Diederich, M. (2011) Antioxidant and anti-proliferative properties of lycopene. Free Radic. Res. 45, 925-940. https://doi.org/10.3109/10715762.2011.564168
  21. Krinsky, N. I. (1998) The antioxidant and biological properties of the carotenoids. Ann. N.Y. Acad. Sci. 854, 443-447. https://doi.org/10.1111/j.1749-6632.1998.tb09923.x
  22. Li, Y., Xue, F., Xu, S. Z., Wang, X. W., Tong, X. and Lin, X. J. (2014) Lycopene protects bone marrow mesenchymal stem cells against ischemia-induced apoptosis in vitro. Eur. Rev. Med. Pharmacol. Sci. 18, 1625-1631.
  23. Los, M., Mozoluk, M., Ferrari, D., Stepczynska, A., Stroh, C., Renz, A., Herceg, Z., Wang, Z. Q. and Schulze-Osthoff, K. (2002) Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol. Biol. Cell 13, 978-988. https://doi.org/10.1091/mbc.01-05-0272
  24. Monsel, A., Zhu, Y. G., Gennai, S., Hao, Q., Liu, J. and Lee, J. W. (2014) Cell-based therapy for acute organ injury: preclinical evidence and ongoing clinical trials using mesenchymal stem cells. Anesthesiology 121, 1099-1121. https://doi.org/10.1097/ALN.0000000000000446
  25. Nakka, V. P., Gusain, A., Mehta, S. L. and Raghubir, R. (2008) Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities. Mol. Neurobiol. 37, 7-38. https://doi.org/10.1007/s12035-007-8013-9
  26. Palozza, P., Parrone, N., Simone, R. E. and Catalano, A. (2010) Lycopene in atherosclerosis prevention: an integrated scheme of the potential mechanisms of action from cell culture studies. Arch. Biochem. Biophys. 504, 26-33. https://doi.org/10.1016/j.abb.2010.06.031
  27. Palozza, P., Simone, R., Catalano, A., Monego, G., Barini, A., Mele, M. C., Parrone, N., Trombino, S., Picci, N. and Ranelletti, F. O. (2011) Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-kappaB nuclear binding and increase in PPARgamma expression. J. Nutr. Biochem. 22, 259-268. https://doi.org/10.1016/j.jnutbio.2010.02.003
  28. Rodrigo, R., Gonzalez, J. and Paoletto, F. (2011) The role of oxidative stress in the pathophysiology of hypertension. Hypertens. Res. 34, 431-440. https://doi.org/10.1038/hr.2010.264
  29. Shi, J. and Le Maguer, M. (2000) Lycopene in tomatoes: chemical and physical properties affected by food processing. Crit. Rev. Food Sci. Nutr. 40, 1-42. https://doi.org/10.1080/10408690091189275
  30. Suncion, V. Y., Ghersin, E., Fishman, J. E., Zambrano, J. P., Karantalis, V., Mandel, N., Nelson, K. H., Gerstenblith, G., DiFede Velazquez, D. L., Breton, E., Sitammagari, K., Schulman, I. H., Taldone, S. N., Williams, A. R., Sanina, C., Johnston, P. V., Brinker, J., Altman, P., Mushtaq, M., Trachtenberg, B., Mendizabal, A. M., Tracy, M., Da Silva, J., McNiece, I. K., Lardo, A. C., George, R. T., Hare, J. M. and Heldman, A. W. (2014) Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial. Circ. Res. 114, 1292-1301. https://doi.org/10.1161/CIRCRESAHA.114.302854
  31. Sung, L. C., Chao, H. H., Chen, C. H., Tsai, J. C., Liu, J. C., Hong, H. J., Cheng, T. H. and Chen, J. J. (2015) Lycopene inhibits cyclic strain-induced endothelin-1 expression through the suppression of reactive oxygen species generation and induction of heme oxygenase-1 in human umbilical vein endothelial cells. Clin. Exp. Pharmacol. Physiol. 42, 632-639. https://doi.org/10.1111/1440-1681.12412
  32. Weyhenmeyer, B., Murphy, A. C., Prehn, J. H. and Murphy, B. M. (2012) Targeting the anti-apoptotic Bcl-2 family members for the treatment of cancer. Exp. Oncol. 34, 192-199.
  33. Yang, T. M., Barbone, D., Fennell, D. A. and Broaddus, V. C. (2009) Bcl-2 family proteins contribute to apoptotic resistance in lung cancer multicellular spheroids. Am. J. Respir. Cell Mol. Biol. 41, 14-23. https://doi.org/10.1165/rcmb.2008-0320OC

Cited by

  1. Insulin as a Potent Stimulator of Akt, ERK and Inhibin-βE Signaling in Osteoblast-Like UMR-106 Cells vol.24, pp.6, 2016, https://doi.org/10.4062/biomolther.2016.030
  2. Protective Effect of Selenoprotein X Against Oxidative Stress-Induced Cell Apoptosis in Human Hepatocyte (LO2) Cells via the p38 Pathway 2017, https://doi.org/10.1007/s12011-017-1025-z
  3. Higher serum lycopene is associated with reduced prevalence of hypertension in overweight or obese adults vol.13, 2017, https://doi.org/10.1016/j.eujim.2017.07.002
  4. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury vol.8, pp.3, 2016, https://doi.org/10.3390/nu8030138
  5. Fluoxetine protects against IL-1β-induced neuronal apoptosis via downregulation of p53 vol.107, 2016, https://doi.org/10.1016/j.neuropharm.2016.03.019
  6. Exposure to chronic hyperglycemic conditions results in Ras-related C3 botulinum toxin substrate 1 (Rac1)-mediated activation of p53 and ATM kinase in pancreatic β-cells vol.22, pp.5, 2017, https://doi.org/10.1007/s10495-017-1354-6
  7. TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts vol.21, pp.9, 2017, https://doi.org/10.1111/jcmm.13131
  8. Selenoprotein X Gene Knockdown Aggravated H2O2-Induced Apoptosis in Liver LO2 Cells vol.173, pp.1, 2016, https://doi.org/10.1007/s12011-016-0653-z
  9. Emerging Importance of Phytochemicals in Regulation of Stem Cells Fate via Signaling Pathways 2017, https://doi.org/10.1002/ptr.5908
  10. Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo pp.15821838, 2018, https://doi.org/10.1111/jcmm.13835
  11. Cytoprotective Roles of a Novel Compound, MHY-1684, against Hyperglycemia-Induced Oxidative Stress and Mitochondrial Dysfunction in Human Cardiac Progenitor Cells vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/4528184
  12. Vaspin protects mouse mesenchymal stem cells from oxidative stress-induced apoptosis through the MAPK/p38 pathway vol.462, pp.1, 2015, https://doi.org/10.1007/s11010-019-03614-8
  13. Neuroprotective Effects of Fluoxetine Against Chronic Stress-Induced Neural Inflammation and Apoptosis: Involvement of the p38 Activity vol.11, pp.None, 2015, https://doi.org/10.3389/fphys.2020.00351
  14. Protective effects of lycopene in cancer, cardiovascular, and neurodegenerative diseases: An update on epidemiological and mechanistic perspectives vol.155, pp.None, 2015, https://doi.org/10.1016/j.phrs.2020.104730
  15. Lycopene antagonizes lead toxicity by reducing mitochondrial oxidative damage and mitochondria‐mediated apoptosis in cultured hippocampal neurons vol.1, pp.2, 2015, https://doi.org/10.1002/mco2.17
  16. Lycopene attenuates high glucose-mediated apoptosis in MPC5 podocytes by promoting autophagy via the PI3K/AKT signaling pathway vol.20, pp.3, 2020, https://doi.org/10.3892/etm.2020.8999
  17. Cytoprotective effects of antioxidant supplementation on mesenchymal stem cell therapy vol.235, pp.10, 2015, https://doi.org/10.1002/jcp.29660
  18. γ- and δ-Tocotrienols interfere with senescence leading to decreased viability of cells vol.476, pp.2, 2015, https://doi.org/10.1007/s11010-020-03954-w
  19. Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction vol.12, pp.6, 2021, https://doi.org/10.1038/s41419-021-03610-1
  20. Spontaneous apoptosis of cells in therapeutic stem cell preparation exert immunomodulatory effects through release of phosphatidylserine vol.6, pp.1, 2015, https://doi.org/10.1038/s41392-021-00688-z