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

Jeong,Min-Ho; Lee,Chang-Min; Lee,Sang-Wha; Seo,Su-Yeong; Seo,Min-Jeong; Kang,Byoung-Won; Jeong,Yong-Kee; Choi,Yoo-Jin; Yang,Kwang-Mo; Jo,Wol-Soon

doi:10.3892/or.2013.2660

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
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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
Published online on: August 6, 2013 https://doi.org/10.3892/or.2013.2660
Pages: 1996-2002

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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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