Cancer Chemotherapy and Pharmacology

, Volume 60, Issue 1, pp 103–111

The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line

  • Wei-Ciao Wu
  • Jenn-Ren Hsiao
  • Yu-Yan Lian
  • Chun-Yu Lin
  • Bu-Miin Huang
Original Article

Abstract

Cordycepin (3′-deoxyadenosine), a pure compound of Cordyceps sinensis, has been illustrated with anti-tumor effects. In the present study, the apoptotic effect of cordycepin on OEC-M1, a human oral squamous cancer cell line, was investigated by morphological observations, cell viability assay, annexin V-FITC analysis and flow cytometry methods. Results demonstrated that the number of rounded-up cell increased as treatment duration of cordycepin (100 μM) increased from 3 to 48 h, and the plasma membrane blebbing could be observed after 12 h treatment. In cell viability assay, cell surviving rate significantly decreased as the dosage and duration of cordycepin treatment increased (< 0.05). Moreover, phosphatidylserine flipping on cell membrane could be detected with 3, 6 and 12 h cordycepin treatment, which indicated an early apoptotic phenomenon. Furthermore, cell cycle studies illustrated that the percentage of G1 phase cell declined as the dosages of cordycepin increased (10 μM to 5 mM), while the percentages of G2M and subG1 phase cell increased (< 0.05) in 12, 24 and 48 h cordycepin treatment. These results further confirmed the apoptotic event. In conclusion, cordycepin significantly induced cell apoptotsis in OEC-M1 human oral squamous cancer cells.

Keywords

Cordycepin Apoptosis OEC-M1 Oral cancer Cell cycle Cell viability 

References

  1. Cui XM (1999) Asia-Pacific Biotech news 3:333–337Google Scholar
  2. Cunningham KG, Hutchinson SA, Manson W, Spring FS (1950) Cordycepin, a metabolic product isolated from cultures of Cordyceps militaris. Nature 166:949Google Scholar
  3. Colgan DF, Murthy KGK, Zhao W, Prives C, Manley JL (1998) Inhibition of poly (A) polymerase requires p34cdc2/cyclin B phosphorylation of multiple consensus and non-consensus sites. EMBO 17:1053–1062CrossRefGoogle Scholar
  4. Daniel PT, Koert U, Schuppan J (2006) Apoptolidin: induction of apoptosis by a natural product. Angew Chem Int Ed Engl 45:872–893PubMedCrossRefGoogle Scholar
  5. Denizot F, Lang R (1986) Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89:271–277PubMedCrossRefGoogle Scholar
  6. Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85–90PubMedCrossRefGoogle Scholar
  7. Feldmann G (2006) Liver apoptosis. Gastroenterol Clin Biol 30:533–45PubMedCrossRefGoogle Scholar
  8. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Eng J Med 349:2091–2098CrossRefGoogle Scholar
  9. Gupta S (2001) Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci 69:2957–2964PubMedCrossRefGoogle Scholar
  10. Gupta PC, Warnakulasuriya S (2002) Global epidemiology of areca nut usage. Addict Biol 7:77–83PubMedCrossRefGoogle Scholar
  11. Ho PS, Ko YC, Yang YH, Shieh TY, Tsai CC (2002) The incidence of oropharyngeal cancer in Taiwan: an endemic betel quid chewing area. J Oral Pathol Med 31:213–219PubMedCrossRefGoogle Scholar
  12. Kopman G, Reutelingsperger CP, Kuijten GAM, Keehnen RMJ, Pals ST, van Oers MHJ (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84:1415–1420Google Scholar
  13. Jeng JH, Chang MC, Hahn LJ (2001) Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol 37:477–492PubMedCrossRefGoogle Scholar
  14. Jin YT, Tsai ST, Wong TY, Chen FF, Chen RM (1996) Studies on promoting activity of Taiwan betel quid ingredients in hamster buccal pouch carcinogenesis. Eur J Cancer B Oral Oncol 32B:343–346PubMedCrossRefGoogle Scholar
  15. Lallas GC, Courtis N, Havredaki M (2004) K562 cell sensitization to 5-fluorouracil- or interferon-alpha-induced apoptosis via cordycepin (3′-deoxyadenosine): fine control of cell apoptosis via poly(A) polymerase upregulation. Int J Biol Markers 19:58–66PubMedGoogle Scholar
  16. Martincic K, Campbell R, Edwalds-Gilbert G, Souan L, Lotze MT, Milcarek C (1998) Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition. Proc Natl Acad Sci USA 95:11095–11100PubMedCrossRefGoogle Scholar
  17. Nakamura K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M (2006) Antitumor effect of cordycepin (3′-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation. Anticancer Res 26(1A):43–47PubMedGoogle Scholar
  18. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flowcytometry. J Immunol Methods 139:271–279PubMedCrossRefGoogle Scholar
  19. Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB (2003) Mechanisms of taxol resistance related to microtubules. Oncogene 22:7280–7295PubMedCrossRefGoogle Scholar
  20. Psyrri A, Kwong M, DiStasio S, Lekakis L, Kassar M, Sasaki C, Wilson LD, Haffty BG, Son YH, Ross DA, Weinberger PM, Chung GG, Zelterman D, Burtness BA, Cooper DL (2004) Cisplatin, fluorouracil, and leucovorin induction chemotherapy followed by concurrent cisplatin chemoradiotherapy for organ preservation and cure in patients with advanced head and neck cancer: long-term follow-up. J Clin Oncol 22:3061–3069PubMedCrossRefGoogle Scholar
  21. Shneyvays V, Jacobson KA, Li AH, Nawrath H, Zinman T, Isaac A, Shainberg A (2000) Induction of apoptosis in rat cardiocytes by A3 adenosine receptor activation and its suppression by isoproterenol. Exp Cell Res 257:111–126PubMedCrossRefGoogle Scholar
  22. Thomadaki H, Tsiapalis CM, Scorilas A (2005) Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction. Biol Chem 386:471–480PubMedCrossRefGoogle Scholar
  23. Wang BJ, Won SJ, Yu ZR, Su CL (2005) Free radical scavenging and apoptotic effects of cordycepin sinensis ractionated by supercritical carbon dioxide. Food Chem Toxicol 43:543–552PubMedCrossRefGoogle Scholar
  24. Yoshikawa N, Nakamura K, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M (2004) Antitumour activity of cordycepin in mice. Clin Exp Pharmacol Physiol Suppl 2:S51–53CrossRefGoogle Scholar
  25. Zhou X, Meyer CU, Schmidtke P, Zepp F (2002) Effect of cordycepin on interleukin-10 production of human peripheral blood mononuclear cells. Eur J Pharmacol 453:309–317PubMedCrossRefGoogle Scholar
  26. Zieve GW, Roemer EJ (1988) Cordycepin rapidly collapses the intermediate filament networks into juxtanuclear caps in fibroblasts and epidermal cells. Exp Cell Res 177:19–26PubMedCrossRefGoogle Scholar
  27. Zieve GW, Feeney RJ, Roemer EJ (1987) Cordycepin disrupts the microtubule networks and arrests Nil 8 hamster fibroblasts at the onset of mitosis. Cell Motil Cytoskelet 7:337–446CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Wei-Ciao Wu
    • 1
  • Jenn-Ren Hsiao
    • 2
  • Yu-Yan Lian
    • 3
  • Chun-Yu Lin
    • 3
  • Bu-Miin Huang
    • 3
  1. 1.Department of Medicine, College of MedicineNational Cheng Kung UniversityTainanTaiwan, ROC
  2. 2.Department of Otolaryngology, College of MedicineNational Cheng Kung UniversityTainanTaiwan, ROC
  3. 3.Department of Cell Biology and Anatomy, College of MedicineNational Cheng Kung UniversityTainanTaiwan, ROC

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