Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Apoptotic Effects of Cordycepin Through the Extrinsic Pathway and p38 MAPK Activation in Human Glioblastoma U87MG Cells

  • Baik, Ji-Sue (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) ;
  • Mun, Seo-Won (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) ;
  • Kim, Kyoung-Sook (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) ;
  • Park, Shin-Ji (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) ;
  • Yoon, Hyun-Kyoung (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) ;
  • Kim, Dong-Hyun (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University) ;
  • Park, Min-Kyu (Department of Clinical Pharmacology & Therapeutics, College of Medicine, Dong-A University) ;
  • Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University) ;
  • Lee, Young-Choon (Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University)
  • Received : 2015.07.29
  • Accepted : 2015.11.12
  • Published : 2016.02.28
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Abstract

We first demonstrated that cordycepin inhibited cell growth and triggered apoptosis in U87MG cells with wild-type p53, but not in T98G cells with mutant-type p53. Western blot data revealed that the levels of procaspase-8, -3, and Bcl-2 were downregulated in cordycepin-treated U87MG cells, whereas the levels of Fas, FasL, Bak, cleaved caspase-3, -8, and cleaved PARP were upregulated, indicating that cordycepin induces apoptosis by activating the death receptor-mediated pathway in U87MG cells. Cordycepin-induced apoptosis could be suppressed by only SB203580, a p38 MAPK-specific inhibitor. These results suggest that cordycepin triggered apoptosis in U87MG cells through p38 MAPK activation and inhibition of the Akt survival pathway.

Keywords

References

  1. Chang L, Karin M. 2001. Mammalian MAP kinase signaling cascades. Nature 410: 37-40. https://doi.org/10.1038/35065000
  2. Das A, Banik NL, Ray SK. 2008. N-(4-Hydroxyphenyl) retinamide induced both differentiation and apoptosis in human glioblastoma T98G and U87MG cells. Brain Res. 1227: 207-215. https://doi.org/10.1016/j.brainres.2008.06.045
  3. Downward J. 1998. Mechanisms and consequences of activation of protein kinase B/Akt. Curr. Opin. Cell Biol. 10: 262-267. https://doi.org/10.1016/S0955-0674(98)80149-X
  4. Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35: 495-516. https://doi.org/10.1080/01926230701320337
  5. Kwon HY, Kim KS, Baik JS, Moon HI, Lee JW, Kim CH, et al. 2013. Triptolide-mediated apoptosis by suppression of focal adhesion kinase through extrinsic and intrinsic pathways in human melanoma cells. Evid. Based Complement. Altern. Med. 2013: 172548.
  6. Lee SJ, Moon GS, Jung KH, Kim WJ, Moon SK. 2010. C-Jun N-terminal kinase 1 is required for cordycepin-mediated induction of G2/M cell-cycle arrest via p21WAF1 expression in human colon cancer cells. Food Chem. Toxicol. 48: 277-283. https://doi.org/10.1016/j.fct.2009.09.042
  7. Mehta RG, Murillo G, Peng X. 2010. Cancer chemoprevention by natural products: how far have we come? Pharm. Res. 27: 950-961. https://doi.org/10.1007/s11095-010-0085-y
  8. Ohgaki H, Kleihues P. 2008. Epidemiology and etiology of gliomas. Acta Neuropathol. 109: 93-108. https://doi.org/10.1007/s00401-005-0991-y
  9. Strano S, Dell’Orso S, Agostino SD, Fontemaggi G, Sacchi A, Blandino G. 2007. Mutant p53: an oncogenic transcription factor. Oncogene 26: 2212-2219. https://doi.org/10.1038/sj.onc.1210296
  10. Suliman A, Lam A, Datta R, Srivastava RK. 2001. Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and -independent pathways. Oncogene 20: 2122-2133. https://doi.org/10.1038/sj.onc.1204282
  11. Tuli HS, Sharma AK, Sandhu SS, Kashyap D. 2013. Cordycepin: a bioactive metabolite with therapeutic potential. Life Sci. 93: 863-869. https://doi.org/10.1016/j.lfs.2013.09.030
  12. Xia Z, Dicken M, Raingeaud J, Davis RJ, Greenberg ME. 1995. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326-1331. https://doi.org/10.1126/science.270.5240.1326
  13. Yang CH, Kao YH, Huang KS, Wang CY, Lin LW. 2012. Cordyceps militaris and mycelial fermentation induced apoptosis and autophagy of human glioblastoma cells. Cell Death Dis. 3: e431. https://doi.org/10.1038/cddis.2012.172

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