title: A novel protein with anti-metastasis activity on 4T1 carcinoma from medicinal fungus Cordyceps militaris.
abstract: Cordyceps militaris is a famous fungus used in traditional Chinese medicine for nearly one thousand years. And its fruiting body is known to possess anticancer and immunomodulatory activities. This study describes the isolation, characterization, and test of antitumor activity of a C. militaris protein, called here as "C. militaris immunoregulatory protein" (CMIP). CMIP was purified through a three-step chromatographic procedure. The MS analyses showed that CMIP corresponded to an uncharacterized protein (CCM_01955) in the C. militaris transcriptional database. Circular dichroism of CMIP revealed the composition of 35.5% β-sheet, 18.5% α-helix, 17.0% turn and 29.0% random coil. No significant cytotoxicity of CMIP was observed on HeLa, HepG2 and 4T1 tumor cells. However, CMIP demonstrated anti-metastasis activity on a mouse model of 4T1 breast cancer lung metastasis. It reduced the number of tumor nodules in the lung of tumor-bearing mice and prolonged their survival time. Furthermore, proliferation of the 4T1 cells was inhibited by macrophage-CMIP conditioned media. And the mRNA levels of cytokines TNF-α, IL-1β and IL-6 were increased significantly in peritoneal macrophages treated by CMIP. These results reveal the antitumor potential of CMIP, thus reinforcing the importance of biochemical prospecting of C. militaris.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Yu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Ye
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Alok
authors.initials: A
authors.lastname: Shrestha
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Yu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei Province, PR China; State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei Province, PR China. Electronic address: sunhui@whu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D032661:Cordyceps / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005260:Female; D048690:Fruiting Bodies, Fungal / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; C000608257:CMIP protein, Cordyceps militaris; D005656:Fungal Proteins; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Anti-metastasis; CMIP; Cordyceps militaris; Cytokines; Macrophages