蛹虫草中抗肿瘤活性成分及作用机制研究进展
Research Progress on Anti-Tumor Active Ingredients and Anti-Tumor Mechanism of Cordyceps militaris
DOI: 10.12677/HJFNS.2019.84034, PDF,  被引量   
作者: 项 婷, 夏 琛, 沈建福*:浙江大学生物系统工程与食品科学学院,天然产物与人类健康研究中心,浙江 杭州;王超然:中国科学院大连化学物理研究所,辽宁 大连;中科院大化所中国医药城生物医药创新研究院,江苏 泰州
关键词: 蛹虫草生物活性成分细胞凋亡细胞周期免疫调节耐药性细胞敏感性Cordyceps militaris Biological Active Ingredients Apoptosis Cell Cycle Immune Regulation Drug-Resistant Cell Sensitivity
摘要: 蛹虫草作为宝贵的生物资源,在抗肿瘤领域具有一定的食药用价值。本文首先对蛹虫草中具有抗肿瘤作用的活性成分进行整理,例如虫草多糖类物质、核苷类物质、蛋白质类物质以及甾醇类物质等。其次,根据蛹虫草的广谱抗肿瘤作用,对其直接或间接的抗肿瘤作用机制进行分类汇总,主要包含抑制嘌呤、DNA和RNA生物合成及蛋白质翻译、诱导肿瘤细胞凋亡、调控细胞周期、抗肿瘤细胞转移和侵袭、改善免疫调节、增强耐药性细胞的敏感性等。最后,在总结前人研究的基础上,提出了未来在蛹虫草抗肿瘤作用的研究中可能值得继续深入探讨的重点,为蛹虫草抗肿瘤的研究开拓思路。
Abstract: As a valuable biological resource, Cordyceps militaris has certain medicinal value in the field of an-ti-tumor. This article firstly organizes the active ingredients with anti-tumor effects in Cordyceps militaris, such as cordyceps polysaccharides, nucleosides, proteinaceous substances and sterols. Secondly, according to the broad-spectrum anti-tumor effect of Cordyceps militaris, its direct or indirect anti-tumor mechanism is classified and summarized, including inhibition of sputum, DNA and RNA biosynthesis and protein translation, induction of tumor cell apoptosis, regulation of cell cycle, inhibition of tumor cell metastasis and invasion, improvement of immune regulation, en-hancement of sensitivity of drug-resistant cells, and the like. Finally, on the basis of summarizing the previous studies, the paper puts forward the focus of future research on the anti-tumor effect of Cordyceps militaris, and explores the research on anti-tumor of Cordyceps militaris.
文章引用:项婷, 夏琛, 沈建福, 王超然. 蛹虫草中抗肿瘤活性成分及作用机制研究进展[J]. 食品与营养科学, 2019, 8(4): 258-266. https://doi.org/10.12677/HJFNS.2019.84034

参考文献

[1] 黄年来, 林志彬, 陈国良, 等. 中国食药用菌学[M]. 上海: 上海科学技术文献出版社, 2010: 1763.
[2] 高凌飞, 王义祥, 翁伯琦. 蛹虫草工厂化栽培与系列加工技术研究进展[J]. 中国农学通报, 2014, 30(13): 93-101.
[3] 杨昕, 斯陆勤, 涂秩平, 等. 不同产地人工蛹虫草子实体及冬虫夏草中核苷类成分的比较[J]. 医药导报, 2009, 28(10): 1354-1356.
[4] Nakamura, K., Shinozuka, K. and Yoshikawa, N. (2015) Anticancer and Antimetastatic Effects of Cordycepin, an Active Component of Ophiocordyceps sinensis. Journal of Pharmacological Sciences, 127, 53-56.
[Google Scholar] [CrossRef] [PubMed]
[5] 周云, 韩重, 杨威, 等. 蛹虫草核苷体外抗肿瘤实验研究[J]. 今日药学, 2015, 25(4): 233-235+246.
[6] Cunningham, K.G., Manson, W., Spring, F.S., et al. (1950) Cordycepin, a Metabolic Product Isolated from Cultures of Cordyceps militaris (Linn.) Link. Nature, 166, 949-949.
[Google Scholar] [CrossRef] [PubMed]
[7] Xia, Y.L., Luo, F.F., Shang, Y.F., et al. (2017) Fungal Cordycepin Bio-synthesis Is Coupled with the Production of the Safeguard Molecule Pentostatin. Cell Chemical Biology, 24, 1479-1489.
[Google Scholar] [CrossRef] [PubMed]
[8] 樊慧婷, 林洪生. 蛹虫草化学成分及药理作用研究进展[J]. 中国中药杂志, 2013, 38(15): 2549-2552.
[9] 朱丽娜, 刘艳芳, 张红霞, 等. 不同来源的蛹虫草子实体活性成分的比较[J]. 菌物学报, 2018, 37(12): 1695-1706.
[10] 周国海, 张泳, 赵立超, 等. 蛹虫草多糖提取纯化工艺研究[J]. 食品与机械, 2014, 30(5): 220-224.
[11] 黄奕诚, 陈雪香, 贺丽苹, 等. 蛹虫草多糖的纯化及其分子量的测定[J]. 现代食品科技, 2012, 28(8): 1054-1057.
[12] 任大明, 李冬琦, 劳云云. 蛹虫草固体发酵培养基多糖的分离纯化及组成分析[J]. 食品工业科技, 2010, 31(10): 121-123.
[13] Yu, R.M., Song, L.Y., Zhao, Y., et al. (2004) Isolation and Biological Properties of Polysaccharide CPS-1 from Cultured Cordyceps militaris. Fitoterapia, 75, 465-472.
[Google Scholar] [CrossRef] [PubMed]
[14] Yu, R.M., Wang, L., Zhang, H., et al. (2004) Isolation, Purification and Identification of Polysaccharides from Cultured Cordyceps militaris. Fitoterapia, 75, 662-666.
[Google Scholar] [CrossRef] [PubMed]
[15] Yu, R.M., Wang, L., Song, L.Y., et al. (2007) Structural Cha-racterization and Antioxidant Activity of a Polysaccharide from the Fruiting Bodies of Cultured Cordyceps militaris. Carbohydrate Polymers, 70, 430-436.
[Google Scholar] [CrossRef
[16] Chen, X.L., Wu, G.H. and Huang, Z.L. (2013) Structural Analysis and Antioxidant Activities of Polysaccharides from Cultured Cordyceps militaris. International Journal of Biological Macromolecules, 58, 18-22.
[Google Scholar] [CrossRef] [PubMed]
[17] Zhang, A.L., Lu, J.H., Zhang, N., et al. (2010) Extraction, Purification and Anti-Tumor Activity of Polysaccharide from Mycelium of Mutant Cordyceps militaris. Chemical Re-search in Chinese Universities, 26, 798-802.
[18] Lou, X.P., Duan, Y.Q., Yang, W.Y., et al. (2017) Structural Eluci-dation and Immunostimulatory Activity of Polysaccharide Isolated by Subcritical Water Extraction from Cordyceps militaris. Carbohydrate Polymers, 157, 794-802.
[Google Scholar] [CrossRef] [PubMed]
[19] 左锦辉, 贡晓燕, 董银卯, 等. 蛹虫草的活性成分和药理作用及其应用研究进展[J]. 食品科学, 2018, 39(21): 330-339.
[20] 孟泽彬, 陈林会, 韩近雨, 等. 蛹虫草化学活性成分的研究进展[J]. 分子植物育种, 2015, 13(9): 2147-2154.
[21] Yang, Q., Yin, Y.L., Xu, G.J., et al. (2015) A Novel Protein with Anti-Metastasis Activity on 4T1 Carcinoma from Medicinal Fungus Cordyceps militaris. Interna-tional Journal of Biological Macromolecules, 80, 385-391.
[Google Scholar] [CrossRef] [PubMed]
[22] Park, B.T., Na, K.H., Jung, E.C., et al. (2009) Antifungal and Anticancer Activities of a Protein from the Mushroom Cordyceps militaris. Korean Journal of Physiology and Pharmacology, 13, 49-54.
[Google Scholar] [CrossRef] [PubMed]
[23] Zhang, Y.G., Liu, S.C., Liu, H.W., et al. (2009) Cycloaspeptides F and G, Cyclic Pentapeptides from a Cordyceps-Colonizing Isolate of Isariafarinosa. Journal of Natural Products, 72, 1364-1367.
[Google Scholar] [CrossRef] [PubMed]
[24] Isaka, M., Srisanoh, U., Lartpotnmatulee, N., et al. (2007) ES-242 De-rivatives and Cycloheptapeptides from Cordyceps sp. Strains BCC 16173 and BCC 16176. Journal of Natural Products, 70, 1601-1604.
[Google Scholar] [CrossRef] [PubMed]
[25] Park, N.S., Lee, K.S., Sohn, H.D., et al. (2005) Molecular Cloning, Ex-pression, and Characterization of the Cu, Zn Superoxide Dismutase (SOD1) Gene from the Entomopathogenic Fungus Cordyceps militaris. Mycologia, 97, 130-138.
[Google Scholar] [CrossRef] [PubMed]
[26] 阿萨(Md.Asaduzzaman Khan). 白藜芦醇通过调节抗氧化酶活性而呈现抗肿瘤效应[D]: [博士学位论文]. 长沙: 中南大学, 2013.
[27] Choi, J.N., Kim, J., Lee, M.Y., et al. (2010) Metabolomics Revealed Novel Isoflavones and Optimal Cultivation Time of Cordyceps militaris Fermentation. Journal of Agricultural and Food Chemistry, 58, 4258-4267.
[Google Scholar] [CrossRef] [PubMed]
[28] Kim, J.H., Park, D.K., Lee, C.H., et al. (2012) A New Isoflavone Glycitein 7-O-beta-d-Glucoside 4’-O-methylate, Isolated from Cordyceps militaris Grown on Germinated Soybeans Extract, Inhibits EGF-Induced Mucus Hypersecretion in the Human Lung Mucoepidermoid Cells. Phytotherapy Research, 26, 1807-1812.
[Google Scholar] [CrossRef] [PubMed]
[29] Khadem, H.S.E. and Ashry, E.S.H.E. (1973) Synthesis of Cordycepin-C [8-(3’-deoxy-β-D-erythro-pentofuranosyl) Adenine. Carbohydrate Research, 29, 525-527.
[Google Scholar] [CrossRef
[30] Hansen, O.K. (1964) The Inhibition of 5-Phosphoribosyl-1-Pyrophosphate Formation by Cordycepin Triphosphate in Extracts of Ehrlich Ascites Tumor Cells. Biochimica et Biophysica Acta, 80, 504-507.
[Google Scholar] [CrossRef] [PubMed]
[31] Kako, K., Hayakawa, H., Tanaka, H., et al. (1997) A New Entry to 2-Substituted Purine Nucleosides Based on Lithiation-Mediated Stannyl Transfer of 6-Chlooropurine Nucleo-sides. The Journal of Organic Chemistry, 60, 6833-6941.
[Google Scholar] [CrossRef
[32] Chen, L.S., Stellrecht, C.M. and Gandhi, V. (2008) RNA-Directed Agent, Cordycepin, Induces Cell Death in Multiple Myeloma Cells. British Journal of Haematology, 140, 682-391.
[Google Scholar] [CrossRef] [PubMed]
[33] Mei, Y.X., Yang, W., Zhu, P.X., et al. (2014) Isolation, Characterization, and Antitumor Activity of a Novel Heteroglycan from Cultured Mycelia of Cordyceps sinensis. Planta Medica, 80, 1107-1112.
[Google Scholar] [CrossRef] [PubMed]
[34] Jeong, J.W., Jin, C.Y., Park, C., et al. (2011) Induction of Apoptosis by Cordycepin via Reactive Oxygen Species Generation in Human Leukemia Cells. Toxicology in Vitro, 25, 817-824.
[Google Scholar] [CrossRef] [PubMed]
[35] Imesch, P., Goerens, A., Fink, D., et al. (2012) MLH1-Deficient HCT116 Colon Tumor Cells Exhibit Resistance to the Cytostatic and Cytotoxic Effect of the Poly(A) Polymerase Inhibitor Cordycepin (3’-deoxyadenosine) in Vitro. Oncology Letters, 3, 441-444.
[Google Scholar] [CrossRef] [PubMed]
[36] Jung, S.M., Psrk, S.S., Kim, W.J., et al. (2012) Ras/ERK1 Pathway Regulation of p27KIP1-Mediated G1-Phase Cell-Cycle Arrest in Cordycepin-Induced Inhibition of the Proliferation of Vascular Smooth Muscle Cells. European Journal of Pharmacology, 681, 15-22.
[Google Scholar] [CrossRef] [PubMed]
[37] 廖园洪. 小分子化合物抑制白血病细胞生长的分子机制研究[D]: [博士学位论文]. 上海: 上海交通大学, 2015.
[38] 韩小娟. 虫草多糖药理活性及机制研究的进展[J]. 医学综述, 2014, 20(16): 3008-3010.
[39] 岳冬梅, 王林美, 李树英. 柞蚕蛹虫草水提物对人乳腺癌细胞MCF-7增殖和凋亡的影响[J]. 中国蚕业, 2014, 35(3): 23-26.
[40] 刘特思, 吕游, 闫文帝, 等. 虫草素通过ERK1/2、Ezrin和Akt信号通路抑制胆囊癌细胞SNU-308的增殖和迁移[J]. 中国病理生理杂志, 2018, 34(8): 1434-1442.
[41] Jayakimar, T., Chiu, C.C., Wang, S.H., et al. (2014) Anti-Cancer Effects of CME-1, a Novel Polysaccharide, Purified from the Mycelia of Cordyceps sinensis against B16-F10 Melanoma Cells. Journal of Cancer Research and Therapeutics, 10, 43-49.
[Google Scholar] [CrossRef] [PubMed]
[42] Jeong, J.W., Jin, C.Y., Park, C., et al. (2012) Inhibition of Migration and Invasion of LNCa P Human Prostate Carcinoma Cells by Cordycepin through Inactivation of Akt. International Journal of Oncology, 40, 1697-1704.
[43] Golubovskaya, V. and Wu, L.J. (2016) Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy. Cancers, 8, 36.
[Google Scholar] [CrossRef] [PubMed]
[44] 诸葛定娟, 程敏, 董文彬, 等. 虫草多糖对荷瘤小鼠T淋巴细胞及其亚群数量与功能的影响[J]. 中国现代应用药学, 2016, 33(5): 528-533.
[45] 叶小弟, 郑高利. 冬虫夏草及其菌丝体多糖免疫药理学研究进展[J]. 中国中医药科技, 2014, 21(1): 107-109.
[46] Nakayama, H. (2014) Overex-pression of Fibronectin Confers Cell Adhesion? Mediated Drug Resistance (CAM-DR) against 5-FU in Oral Squamous Cell Carcinoma Cells. International Journal of Oncology, 44, 1376-1384.
[Google Scholar] [CrossRef] [PubMed]
[47] Li, D.H., Pan, Z.K., Ye, F., et al. (2014) S-1-Based versus 5-FU-Based Chemotherapy as First-Line Treatment in Advanced Gastric Cancer: A Meta-Analysis of Randomized Controlled Trials. Tumor Biology, 35, 8201-8208.
[Google Scholar] [CrossRef] [PubMed]
[48] Guo, X.L., Hu, F., Zhang, S.S., et al. (2014) Inhibition of p53 Increases Chemosensitivity to 5-FU in Nutrient-Deprived Hepatocarcinoma Cells by Suppressing Autophagy. Cancer Letters, 346, 278-284.
[Google Scholar] [CrossRef] [PubMed]
[49] Ducreux, M., Dahan, L., Smith, D., et al. (2014) Bevacizumab Combined with 5-FU/Streptozocin in Patients with Progressive Metastatic Well-Differentiated Pancreatic Endocrine Tumours (BETTER Trial): A Phase II Non-Randomised Trial. European Journal of Cancer, 50, 3098-3106.
[Google Scholar] [CrossRef] [PubMed]
[50] Zhang, H.H., Tang, J.L., Li, C., et al. (2015) MiR-22 Regulates 5-FU Sensitivity by Inhibiting Autophagy and Promoting Apoptosis in Colorectal Cancer Cells. Cancer Letters, 356, 781-790.
[Google Scholar] [CrossRef] [PubMed]
[51] Folprecht, G., Pericay, C., Saunders, M.P., et al. (2016) Oxa-liplatin and 5-FU/Folinic Acid (Modified FOLFOX6) with or without Aflibercept in First-Line Treatment of Patients with Metastatic Colorectal Cancer: The AFFIRM Study. Annals of Oncology, 27, 1273-1279.
[Google Scholar] [CrossRef] [PubMed]
[52] Li, X.R., Wang, S.X., Li, Z.Z., et al. (2017) Retracted: NEAT1 Induces Epithelial-Mesenchymal Transition and 5-FU Resistance through the miR-129/ZEB2 Axis in Breast Cancer. FEBS Letters, 591, 570-570.
[Google Scholar] [CrossRef] [PubMed]
[53] Hainsworth, J.D., Meluch, A.A., Mcclurkan, S., et al. (2002) In-duction Paclitaxel, Carboplatin, and Infusional 5-FU Followed by Concurrent Radiation Therapy and Weekly Paclitax-el/Carboplatin in the Treatment of Locally Advanced Head and Neck Cancer. The Cancer Journal, 8, 311-321.
[Google Scholar] [CrossRef] [PubMed]
[54] 付楚溪, 焦阳, 李思雨, 等. 蛹虫草中虫草素抗癌活性研究进展[J]. 食品安全导刊, 2015(9X): 155-157.
[55] 张楠, 逄利, 凡文博, 等. 蛹虫草小分子肽增强胃癌细胞株SGC-7901对氟尿嘧啶化疗的敏感性[J]. 中国老年学杂志, 2015, 35(13): 3520-3521.