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

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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 (P < 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 (P < 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.

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References

  • Cui XM (1999) Asia-Pacific Biotech news 3:333–337

    Google Scholar 

  • Cunningham KG, Hutchinson SA, Manson W, Spring FS (1950) Cordycepin, a metabolic product isolated from cultures of Cordyceps militaris. Nature 166:949

    Google Scholar 

  • 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 17:1053–1062

    Article  CAS  Google Scholar 

  • Daniel PT, Koert U, Schuppan J (2006) Apoptolidin: induction of apoptosis by a natural product. Angew Chem Int Ed Engl 45:872–893

    Article  PubMed  CAS  Google Scholar 

  • 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 89:271–277

    Article  PubMed  CAS  Google Scholar 

  • Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85–90

    Article  PubMed  CAS  Google Scholar 

  • Feldmann G (2006) Liver apoptosis. Gastroenterol Clin Biol 30:533–45

    Article  PubMed  CAS  Google Scholar 

  • 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 349:2091–2098

    Article  CAS  Google Scholar 

  • Gupta S (2001) Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci 69:2957–2964

    Article  PubMed  CAS  Google Scholar 

  • Gupta PC, Warnakulasuriya S (2002) Global epidemiology of areca nut usage. Addict Biol 7:77–83

    Article  PubMed  CAS  Google Scholar 

  • 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 31:213–219

    Article  PubMed  Google Scholar 

  • 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 84:1415–1420

    Google Scholar 

  • Jeng JH, Chang MC, Hahn LJ (2001) Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol 37:477–492

    Article  PubMed  CAS  Google Scholar 

  • 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:343–346

    Article  PubMed  CAS  Google Scholar 

  • 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 19:58–66

    PubMed  CAS  Google Scholar 

  • 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 95:11095–11100

    Article  PubMed  CAS  Google Scholar 

  • 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):43–47

    PubMed  CAS  Google Scholar 

  • 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 139:271–279

    Article  PubMed  CAS  Google Scholar 

  • Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB (2003) Mechanisms of taxol resistance related to microtubules. Oncogene 22:7280–7295

    Article  PubMed  CAS  Google Scholar 

  • 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 22:3061–3069

    Article  PubMed  CAS  Google Scholar 

  • 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 257:111–126

    Article  PubMed  CAS  Google Scholar 

  • 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 386:471–480

    Article  PubMed  CAS  Google Scholar 

  • 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 43:543–552

    Article  PubMed  CAS  Google Scholar 

  • 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:S51–53

    Article  Google Scholar 

  • 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 453:309–317

    Article  PubMed  CAS  Google Scholar 

  • Zieve GW, Roemer EJ (1988) Cordycepin rapidly collapses the intermediate filament networks into juxtanuclear caps in fibroblasts and epidermal cells. Exp Cell Res 177:19–26

    Article  PubMed  CAS  Google Scholar 

  • 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 7:337–446

    Article  CAS  Google Scholar 

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Acknowledgment

This study was supported by the National Science Council NSC95-2320-B-006-059-MY3 to BMH, Taiwan, ROC.

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Authors and Affiliations

  1. Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

    Wei-Ciao Wu

  2. Department of Otolaryngology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

    Jenn-Ren Hsiao

  3. Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, #1 University Road, Tainan, 70101, Taiwan, ROC

    Yu-Yan Lian, Chun-Yu Lin & Bu-Miin Huang

Authors
  1. Wei-Ciao Wu
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  2. Jenn-Ren Hsiao
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  3. Yu-Yan Lian
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  4. Chun-Yu Lin
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  5. Bu-Miin Huang
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Correspondence to Bu-Miin Huang.

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Wei-Ciao Wu and Jenn-Ren Hsiao contributed equally.

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Wu, WC., Hsiao, JR., Lian, YY. et al. The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line. Cancer Chemother Pharmacol 60, 103–111 (2007). https://doi.org/10.1007/s00280-006-0354-y

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  • DOI: https://doi.org/10.1007/s00280-006-0354-y

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