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http://dx.doi.org/10.4062/biomolther.2015.085

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)
Publication Information
Biomolecules & Therapeutics / v.23, no.6, 2015 , pp. 517-524 More about this Journal
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
Lycopene; MSC; Oxidative stress; Apoptosis; Anti-oxidant reagent;
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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.   DOI
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.   DOI
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.   DOI
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.   DOI
7 Cohen, G. M. (1997) Caspases: the executioners of apoptosis. Biochem. J. 326, 1-16.   DOI
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.   DOI
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.   DOI
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.   DOI
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 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.   DOI
15 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.   DOI
16 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.   DOI
17 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.   DOI
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.   DOI
19 Kelkel, M., Schumacher, M., Dicato, M. and Diederich, M. (2011) Antioxidant and anti-proliferative properties of lycopene. Free Radic. Res. 45, 925-940.   DOI
20 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.   DOI
21 Krinsky, N. I. (1998) The antioxidant and biological properties of the carotenoids. Ann. N.Y. Acad. Sci. 854, 443-447.   DOI
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.   DOI
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.   DOI
25 Rodrigo, R., Gonzalez, J. and Paoletto, F. (2011) The role of oxidative stress in the pathophysiology of hypertension. Hypertens. Res. 34, 431-440.   DOI
26 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.   DOI
27 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.   DOI
28 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.   DOI
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.   DOI
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.   DOI
31 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.   DOI
32 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.   DOI
33 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.