Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.
OBJECTIVE
To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.


METHODS
Cell counting and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt) method were used to monitor the effects of cordycepin on cell proliferation. Flow cytometry (FCM) was used to analyze the effects of cordycepin on the cell cycle progress. Annexin V-fluorescein isothiocyanate (FITC) analysis was used to detect apoptosis at a very early stage. Caspase-Glo was used to determine caspase activity and Western blot was used to measure protein expression levels of c-Jun N-terminal kinase (JNK), p38, and Bcl-2 pro-apoptosis family.


RESULTS
The numbers of viable SW480 and SW620 cells and the proliferation of these cells were significantly reduced with increases in cordycepin concentration (P<0.01). The cell cycle progression of SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin, and apoptosis rates of cordycepin treatments were increased compared with the control group. Cordycepin-treated cells showed phosphatidylserine valgus, suggesting the existence of early apoptosis. Caspase-3/7 and -9 activity significantly increased and the protein expression levels of JNK, p38, and Bax, Bid, Bim, and Puma from Bcl-2 pro-apoptosis molecules also increased after the treatment with cordycepin.


CONCLUSIONS
Cordycepin can inhibit SW480 and SW620 cell proliferation and induce apoptosis. Apoptosis might be induced by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.
He
Wei
W
The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. heweihz@126.com
Zhang
Mei-fang
MF
Ye
Jun
J
Jiang
Ting-ting
TT
Fang
Xu
X
Song
Ying
Y
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D003839:Deoxyadenosines / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D019253:Proto-Oncogene Proteins c-bcl-2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C058120:cordycepin
Curr Opin Cell Biol. 2005 Dec;17(6):617-25
16243507
J Biol Chem. 2010 Jan 22;285(4):2610-21
19940154
Oncogene. 2007 May 14;26(22):3291-310
17496923
Cancer Chemother Pharmacol. 2008 Feb;61(2):251-65
17487491
Am J Chin Med. 2008;36(5):967-80
19051361
Evid Based Complement Alternat Med. 2011;2011:984537
19131393
Arch Biochem Biophys. 2009 Oct 15;490(2):103-9
19733546
Int J Biol Markers. 2004 Jan-Mar;19(1):58-66
15077928
J Clin Invest. 2004 Apr;113(7):960-2
15057301
Life Sci. 2004 Apr 23;74(23):2897-908
15050427
Lancet Oncol. 2005 Jul;6(7):444-5
15992692
Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):347-53
18806893
Oncogene. 2003 Nov 24;22(53):8590-607
14634621
In Vivo. 2005 Jan-Feb;19(1):137-41
15796166
Biochem Pharmacol. 2000 Feb 1;59(3):273-81
10609556
FASEB J. 2004 Dec;18(15):1946-8
15388671
Eur J Pharmacol. 2006 Sep 18;545(2-3):192-9
16899239
J Microbiol Biotechnol. 2007 Jul;17(7):1134-8
18051324
Oncogene. 2005 Jun 2;24(24):3886-95
15856031
Anticancer Res. 2007 Sep-Oct;27(5A):3143-6
17970055
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):591-5
18084742
Biochemistry. 1991 Feb 26;30(8):2027-33
1705437
Food Chem Toxicol. 2005 Apr;43(4):543-52
15721201
Phytomedicine. 2007 Jan;14(1):43-9
16423520
J Cereb Blood Flow Metab. 2005 Jun;25(6):694-712
15716857
Science. 1995 Nov 24;270(5240):1326-31
7481820
Eur J Pharmacol. 2008 Nov 12;597(1-3):64-9
18782572
Br J Haematol. 2008 Mar;140(6):682-391
18205859
Phytochemistry. 2008 May;69(7):1469-95
18343466