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Article

Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer

  • Authors:
    • Min-Ho Jeong
    • Chang-Min Lee
    • Sang-Wha Lee
    • Su-Yeong Seo
    • Min-Jeong Seo
    • Byoung-Won Kang
    • Yong-Kee Jeong
    • Yoo-Jin Choi
    • Kwang-Mo Yang
    • Wol-Soon Jo
  • View Affiliations / Copyright

    Affiliations: Department of Microbiology, Dong-A University College of Medicine, Busan 604-714, Republic of Korea, Medi-Farm Industrialization Research Center, Dong-A University, Busan 604-714, Republic of Korea, Department of Research Center, Dong Nam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea
  • Pages: 1996-2002
    |
    Published online on: August 6, 2013
       https://doi.org/10.3892/or.2013.2660
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Abstract

Cordyceps militaris (C. militaris) and its main functional component, cordycepin, has been shown to possess a number of pharmacological activities including immunological stimulation and antitumor effects. However, the pharmacological mechanisms of C. militaris on tumor immunity underlying its antitumor effect have yet to be elucidated. In the present study, we evaluated the antitumor and immunomodulatory effects of C. militaris on FM3A tumor-bearing C3H/He mice, comparing wild-type C. militaris and cordycepin-enriched C. militaris (JLM 0636). The concentration of cordycepin produced by crossbred JLM 0636 was 7.42 mg/g dry weight, which was 7-fold higher than that of wild-type C. militaris. Dietary administration of C. militaris revealed retardation of tumor growth as well as elongation of survival rates of tumor-bearing mice. This effect was more pronounced in JLM 0636. There was a cordycepin-dependent decrease in IL-2 and TGF-β secretion and an increase in IL-4 secretion without changes in the proliferative responses of concanavalin A-stimulated lymphocytes, which suggested that C. militaris feeding might induce changes in the subpopulations of tumor-derived T lymphocytes. CD4+CD25+ cell population was significantly reduced in the total splenocytes from JLM 0636-administered mice, while CD4+ T cell population remained unchanged. FoxP3+-expressing Treg cells among CD4+CD25+ population showed a similar pattern. On the contrary, CD8+ T cells as well as the IFN-γ expressing CD8+ T cells from tumor-bearing mice were significantly upregulated by the administration of JLM 0636. These results demonstrated the suppressive role of JLM 0636 on the function of Treg cells contributing to tumor specific IFN-γ-expressing CD8+ T cell responses in tumor-bearing mice, which explained the underlying mechanism of the antitumor immunity of cordycepin. Therefore, cordycepin-enriched C. militaris is a promising candidate for an adjuvant in cancer immunotherapy.
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1 

Cunningham KG, Manson W, Spring FS and Hutchinson SA: Cordycepin, a metabolic product isolated from cultures of Cordyceps militaris (Linn.). Nature. 166:9491950. View Article : Google Scholar : PubMed/NCBI

2 

Paterson RR: Cordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry. 69:1469–1495. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Kim HG, Shrestha B, Lim SY, et al: Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur J Pharmacol. 545:192–199. 2006.PubMed/NCBI

4 

Yun Y, Han S, Lee S, Ko S, Lee C, Ha N and Kim K: Anti-diabetic effects of CCCA, CMESS, and cordycepin from Cordyceps militaris and the immune responses in streptozotocin-induced diabetic mice. Nat Prod Sci. 9:291–298. 2003.

5 

Ahn YJ, Park SJ, Lee SG, Shin SC and Choi DH: Cordycepin: selective growth inhibitor derived from liquid culture of Cordyceps militaris against Clostridium spp. J Agric Food Chem. 48:2744–2748. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Sugar AM and McCaffrey RP: Antifungal activity of 3′-deoxyadenosine (cordycepin). Antimicrob Agents Chemother. 42:1424–1427. 1998.

7 

Müller WE, Weiler BE, Charubala R, et al: Cordycepin analogues of 2′,5′-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase. Biochemistry. 30:2027–2033. 1991.

8 

Kodama EN, McCaffrey RP, Yusa K and Mitsuya H: Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells. Biochem Pharmacol. 59:273–281. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Cho MA, Lee DS, Kim MJ, Sung JM and Ham SS: Antimutagenicity and cytotoxicity of cordycepin isolated from Cordyceps militaris. Food Sci Biotechnol. 12:472–475. 2003.

10 

Nakamura K, Konoha K, Yoshikawa N, Yamaguch Y, Kagota S, Shinozuka K and Kunitomo M: Effect of cordycepin (3′-deoxyadenosine) on hematogenic lung metastatic model mice. In Vivo. 19:137–141. 2005.

11 

Nakamura K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K and Kunitomo M: Antitumor effect of cordycepin (3′-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation. Anticancer Res. 26:43–48. 2006.

12 

Thomadaki H, Scorilas A, Tsiapalis CM and Havredaki M: The role of cordycepin in cancer treatment via induction or inhibition of apoptosis: implication of polyadenylation in a cell type specific manner. Cancer Chemother Pharmacol. 61:251–265. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Jeong JW, Jin CY, Park C, et al: Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells. Toxicol In Vitro. 25:817–824. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Odunsi K and Old LJ: Tumor infiltrating lymphocytes: indicators of tumor-related immune responses. Cancer Immun. 7:32007.PubMed/NCBI

15 

Zou W: Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 5:263–274. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Jeong MH, Seo MJ, Park JU, et al: Effect of cordycepin purified from Cordyceps militaris on Th1 and Th2 cytokines in mouse splenocytes. J Microbiol Biotechnol. 22:1161–1164. 2012.PubMed/NCBI

17 

Zou W: Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 6:295–307. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Curiel TJ: Regulatory T cells and treatment of cancer. Curr Opin Immunol. 20:241–246. 2008. View Article : Google Scholar

19 

Liu Z, Kim JH, Falo LDJ and You Z: Tumor regulatory T cells potently abrogate antitumor immunity. J Immunol. 182:6160–6167. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Malmberg KJ: Effective immunotherapy against cancer: a question of overcoming immune suppression and immune escape? Cancer Immunol Immunother. 53:879–892. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Horowitz B, Goldfinger BA and Marmur J: Effect of cordycepin triphosphate on the nuclear DNA-dependent RNA polymerases and poly(A) polymerase from the yeast, Saccharomyces cerevisiae. Arch Biochem Biophys. 172:143–148. 1976. View Article : Google Scholar : PubMed/NCBI

22 

Muller WE, Seibert G, Beyer R, Breter HJ, Maidhof A and Zahn RK: Effect of cordycepin on nucleic acid metabolism in L5178Y cells and on nucleic acid-synthesizing enzyme systems. Cancer Res. 37:3824–3833. 1977.PubMed/NCBI

23 

Rosenberg SA: Karnofsky Memorial Lecture. The immunotherapy and gene therapy of cancer. J Clin Oncol. 10:180–199. 1992.PubMed/NCBI

24 

von Boehmer H: Mechanisms of suppression by suppressor T cells. Nat Immunol. 6:338–344. 2005.PubMed/NCBI

25 

Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F and Sakaguchi S: Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol. 162:5317–5326. 1999.PubMed/NCBI

26 

Takahashi T, Kuniyasu Y, Toda M, et al: Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol. 10:1969–1980. 1998.

27 

de la Rosa M, Rutz S, Dorninger H and Scheffold A: Interleukin-2 is essential for CD25+CD4+ regulatory T cell function. Eur J Immunol. 34:2480–2488. 2004.PubMed/NCBI

28 

Furtado GC, Curotto de Lafaille MA, Kutchukhidze N and Lafaille JJ: Interleukin 2 signaling is required for CD4+ regulatory T cell function. J Exp Med. 196:851–857. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Yao Z, Kanno Y, Kerenyi M, et al: Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood. 109:4368–4375. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Yamagiwa S, Gray JD, Hashimoto S and Horwitz DA: A role for TGF-β in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol. 166:7282–7289. 2001.

31 

Ghiringhelli F, Puig PE, Roux S, et al: Tumor cells convert immature myeloid dendritic cells into TGF-β-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med. 202:919–929. 2005.PubMed/NCBI

32 

Chen W, Jin W, Hardegen N, et al: Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J Exp Med. 198:1875–1886. 2003.

33 

Valérie D, Amit A, Hyoung K, et al: IL-4 inhibits TGF-β-induced Foxp3+ T cells and, together with TGF-β, generates IL-9+ IL-10+ Foxp3−effector T cells. Nat Immunol. 9:1347–1355. 2008.

34 

Xiaoyu H and Lionel BL: Cross-regulation of signaling pathway by interferon-γ: implication for immune response and autoimmune diseases. Immunity. 31:539–550. 2009.

35 

Chen ML, Pittet MJ, Gorelik L, et al: Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo. Proc Natl Acad Sci. 102:419–424. 2005.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Jeong M, Lee C, Lee S, Seo S, Seo M, Kang B, Jeong Y, Choi Y, Yang K, Jo W, Jo W, et al: Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer. Oncol Rep 30: 1996-2002, 2013.
APA
Jeong, M., Lee, C., Lee, S., Seo, S., Seo, M., Kang, B. ... Jo, W. (2013). Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer. Oncology Reports, 30, 1996-2002. https://doi.org/10.3892/or.2013.2660
MLA
Jeong, M., Lee, C., Lee, S., Seo, S., Seo, M., Kang, B., Jeong, Y., Choi, Y., Yang, K., Jo, W."Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer". Oncology Reports 30.4 (2013): 1996-2002.
Chicago
Jeong, M., Lee, C., Lee, S., Seo, S., Seo, M., Kang, B., Jeong, Y., Choi, Y., Yang, K., Jo, W."Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer". Oncology Reports 30, no. 4 (2013): 1996-2002. https://doi.org/10.3892/or.2013.2660
Copy and paste a formatted citation
x
Spandidos Publications style
Jeong M, Lee C, Lee S, Seo S, Seo M, Kang B, Jeong Y, Choi Y, Yang K, Jo W, Jo W, et al: Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer. Oncol Rep 30: 1996-2002, 2013.
APA
Jeong, M., Lee, C., Lee, S., Seo, S., Seo, M., Kang, B. ... Jo, W. (2013). Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer. Oncology Reports, 30, 1996-2002. https://doi.org/10.3892/or.2013.2660
MLA
Jeong, M., Lee, C., Lee, S., Seo, S., Seo, M., Kang, B., Jeong, Y., Choi, Y., Yang, K., Jo, W."Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer". Oncology Reports 30.4 (2013): 1996-2002.
Chicago
Jeong, M., Lee, C., Lee, S., Seo, S., Seo, M., Kang, B., Jeong, Y., Choi, Y., Yang, K., Jo, W."Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer". Oncology Reports 30, no. 4 (2013): 1996-2002. https://doi.org/10.3892/or.2013.2660
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