Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells

I. Made Winarsa Ruma, Endy Widya Putranto, Eisaku Kondo, Risayo Watanabe, K. E N Saito, Yusuke Inoue, Ken-ichi Yamamoto, Susumu Nakata, Masaji Kaihata, Hitoshi Murata, Masakiyo Sakaguchi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an anti-tumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3β activation, while p38á phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with down regulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors.

Original languageEnglish
Pages (from-to)209-218
Number of pages10
JournalInternational Journal of Oncology
Volume45
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Cordyceps
Melanoma
Growth
Vascular Endothelial Growth Factor Receptor
Neoplasms
Glycogen Synthase Kinase 3
Angiogenesis Inducing Agents
Agaricales
Antineoplastic Agents

Keywords

  • Akt and GSK-3β
  • Angiogenesis
  • Cordyceps militaris
  • Melanoma
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells. / Ruma, I. Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Watanabe, Risayo; Saito, K. E N; Inoue, Yusuke; Yamamoto, Ken-ichi; Nakata, Susumu; Kaihata, Masaji; Murata, Hitoshi; Sakaguchi, Masakiyo.

In: International Journal of Oncology, Vol. 45, No. 1, 2014, p. 209-218.

Research output: Contribution to journalArticle

Ruma, I. Made Winarsa ; Putranto, Endy Widya ; Kondo, Eisaku ; Watanabe, Risayo ; Saito, K. E N ; Inoue, Yusuke ; Yamamoto, Ken-ichi ; Nakata, Susumu ; Kaihata, Masaji ; Murata, Hitoshi ; Sakaguchi, Masakiyo. / Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells. In: International Journal of Oncology. 2014 ; Vol. 45, No. 1. pp. 209-218.
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AU - Inoue, Yusuke

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