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References

  1. Chang L, Karin M. 2001. Mammalian MAP kinase signaling cascades. Nature 410: 37-40.
    Pubmed CrossRef
  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.
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    CrossRef
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    Pubmed PMC CrossRef
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    Pubmed PMC CrossRef
  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.
    Pubmed CrossRef
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    Pubmed CrossRef
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    Pubmed CrossRef
  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.
    Pubmed CrossRef
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    Pubmed PMC CrossRef

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J. Microbiol. Biotechnol. 2016; 26(2): 309-314

Published online February 28, 2016 https://doi.org/10.4014/jmb.1507.07090

Copyright © The Korean Society for Microbiology and Biotechnology.

Apoptotic Effects of Cordycepin Through the Extrinsic Pathway and p38 MAPK Activation in Human Glioblastoma U87MG Cells

Ji-Sue Baik 1, 2, Seo-Won Mun 1, Kyoung-Sook Kim 1, Shin-Ji Park 1, 2, Hyun-Kyoung Yoon 1, Dong-Hyun Kim 1, Min-Kyu Park 3, Cheorl-Ho Kim 4 and Young-Choon Lee 1*

1Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Republic of Korea, 2Department of Clinical Research, Dongnam Institute of Radiological & Medical Sciences Research Center, Busan 46033, Republic of Korea, 3Department of Clinical Pharmacology & Therapeutics, College of Medicine, Dong-A University, Busan 49201, Republic of Korea, 4Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Kyunggi-Do 16419, Republic of Korea

Received: July 29, 2015; Accepted: November 12, 2015

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 cordycepintreated
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: Cordycepin, apoptosis, extrinsic pathway, U87MG cell, p38 MAPK

References

  1. Chang L, Karin M. 2001. Mammalian MAP kinase signaling cascades. Nature 410: 37-40.
    Pubmed CrossRef
  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.
    Pubmed KoreaMed CrossRef
  3. Downward J. 1998. Mechanisms and consequences of activation of protein kinase B/Akt. Curr. Opin. Cell Biol. 10:262-267.
    CrossRef
  4. Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35: 495-516.
    Pubmed KoreaMed CrossRef
  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.
    Pubmed KoreaMed CrossRef
  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.
    Pubmed CrossRef
  7. Mehta RG, Murillo G, Peng X. 2010. Cancer chemoprevention by natural products: how far have we come? Pharm. Res. 27:950-961.
    CrossRef
  8. Ohgaki H, Kleihues P. 2008. Epidemiology and etiology of gliomas. Acta Neuropathol. 109: 93-108.
    Pubmed CrossRef
  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.
    Pubmed CrossRef
  10. Suliman A, Lam A, Datta R, Srivastava RK. 2001. Intracellular mechanisms of TRAIL: apoptosis through mitochondrialdependent and -independent pathways. Oncogene 20: 21222133.
    Pubmed CrossRef
  11. Tuli HS, Sharma AK, Sandhu SS, Kashyap D. 2013. Cordycepin: a bioactive metabolite with therapeutic potential. Life Sci. 93: 863-869.
    Pubmed CrossRef
  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.
    Pubmed CrossRef
  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.
    Pubmed KoreaMed CrossRef