真菌提取物抗肿瘤研究进展

摘要/Abstract

摘要：

本文总结了近几年真菌提取物的抗癌作用相关的研究成果。一方面包括了最近几年关于真菌提取物诱导癌细胞凋亡、抑制癌细胞增生、减少癌细胞血管生成的各种机制研究，另一方面归纳了多种真菌提取物对癌细胞抑制作用的研究结果。近几年的研究结果显示，真菌提取物能够抑制多种肿瘤细胞的增殖，并诱导其凋亡，其机制与Wnt、NK-κB、MAPK、线粒体凋亡等多种信号通路相关，靶点包括了p38、bcl-2、c-jun、IκB、β-catenin、Akt等多种与细胞生物活动密切相关的蛋白。

关键词: 真菌, 肿瘤, 机制, 进展

Abstract:

This review summaries theadvance in anti-cancer fungal extracts in recent years.On the one hand,related multiple mechanisms might include the anti-cancer fungal extracts inducing apoptosis,inhibiting proliferation and angiogenesis.On the other hand,the anti-cancer effects of various anti-cancer fungal extracts in cancer cells are also reviewed.These study show that anti-cancer fungal extracts can inhibit the proliferation of cancer cells and induce apoptosis in cancer cells.The mechanisms of those functions involved various signal pathways,including Wnt,NK-κB,MAPK and Mitochondria related apoptosis signal pathways,and related to various proteins related to biological activity such as p38,bcl-2,c-jun,IκB,β-catenin,Akt.

Key words: fungus, cancer, mechanisms, progresses

中图分类号:

R979.1

曾炫皓, 章强强. 真菌提取物抗肿瘤研究进展[J]. 中国真菌学杂志, 2017, 12(3): 184-192.

ZENG Xuan-hao, ZHANG Qiang-qiang. The recent progresses of anti-cancer fungal extracts[J]. Chinese Journal of Mycology, 2017, 12(3): 184-192.

参考文献

[1] Li C,Wu X,Zhang H,et al.A Huaier polysaccharide reduced metastasis of human hepatocellular carcinoma SMMC-7721 cells via modulating AUF-1 signaling pathway[J].Tumour Biol,2015,36(8):6285-6293.
[2] Zhang X,Ding R,Zhou Y,et al.Toll-like receptor 2 and Toll-like receptor 4-dependent activation of B cells by a polysaccharide from marine fungus Phoma herbarum YS4108[J].PLoS ONE,2013,8(3):e60781.
[3] Li X,Zhao X,Wang H,et al.A polysaccharide from the fruiting bodies of Agaricus blazei Murill induces caspase-dependent apoptosis in human leukemia HL-60 cells[J].Tumour Biol,2014,35(9):8963-8968.
[4] Nagre NN,Chachadi VB,Sundaram PM,et al.A potent mitogenic lectin from the mycelia of a phytopathogenic fungus,Rhizoctonia bataticola,with complex sugar specificity and cytotoxic effect on human ovarian cancer cells[J].Glycoconj J,2010,27(3):375-386.
[5] Barkeer S,Guha N,Hothpet V,et al.Molecular mechanism of anticancer effect of Sclerotium rolfsii lectin in HT29 cells involves differential expression of genes associated with multiple signaling pathways:A microarray analysis[J].Glycobiology,2015,25(12):1375-1391.
[6] Cheng S,Swanson K,Eliaz I,et al.Pachymic acid inhibits growth and induces apoptosis of pancreatic cancer in vitro and in vivo by targeting ER stress[J].PLoS One,2015,10(4):e122270.
[7] Yang F,Chen WD,Deng R,et al.Hirsutanol A,a novel sesquiterpene compound from fungus Chondrostereum sp.,induces apoptosis and inhibits tumor growth through mitochondrial-independent ROS production:hirsutanol A inhibits tumor growth through ROS production[J].J Transl Med,2013,11:32.
[8] Deng Q,Yu X,Xiao L,et al.Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway[J].Cell Death Dis,2013,4:e804.
[9] Gill BS,Kumar S,Navgeet.Ganoderic acid A targeting beta-catenin in Wnt signaling pathway:in silico and in vitro study[J].Interdiscip Sci,2016.
[10] Zhao J,Ma J,Lu J,et al.Involvement of p38MAPK-ATF2 signaling pathway in alternariol induced DNA polymerase beta expression[J].Oncol Lett,2016,12(1):675-679.
[11] Koul M,Meena S,Kumar A,et al.Secondary metabolites from endophytic fungus Penicillium pinophilum induce ROS-mediated apoptosis through mitochondrial pathway in Pancreatic Cancer Cells[J].Planta Med,2016,82(4):344-355.
[12] Tao YW,Lin YC,She ZG,et al.Anticancer activity and mechanism investigation of beauvericin isolated from secondary metabolites of the mangrove endophytic fungi[J].Anticancer Agents Med Chem,2015,15(2):258-266.
[13] Chen J,Wang C,Lan W,et al.Gliotoxin inhibits proliferation and induces apoptosis in Colorectal Cancer Cells[J].Mar Drugs,2015,13(10):6259-6273.
[14] Kim NH,Jung HI,Choi WS,et al.Toluhydroquinone,the secondary metabolite of marine algae symbiotic microorganism,inhibits angiogenesis in HUVECs[J].Biomed Pharmacother,2015,70:129-139.
[15] Ramos AA,Castro-Carvalho B,Prata-Sena M,et al.Crude extracts of marine-derived and soil fungi of the genus neosartorya exhibit selective anticancer activity by inducing cell death in colon,breast and skin cancer cell lines[J].Pharmacognosy Res,2016,8(1):8-15.
[16] Kim HG,Song H,Yoon DH,et al.Cordyceps pruinosa extracts induce apoptosis of HeLa cells by a caspase dependent pathway[J].J Ethnopharmacol,2010,128(2):342-351.
[17] Harms H,Orlikova B,Ji S,et al.Epipolythiodiketopiperazines from the marine derived fungus Dichotomomyces cejpii with NF-kappa B inhibitory potential[J].Mar Drugs,2015,13(8):4949-4966.
[18] Ai W,Wei XY,Lin XP,et al.Guignardins A-F,spirodioxynaphthalenes from the endophytic fungus Guignardia sp KcF8 as a new class of PTP1B and SIRT1 inhibitors[J].TETRAHEDRON,2014,70(35):5806-5814.
[19] Chang HT,Chou CT,Chen IS,et al.Mechanisms underlying effect of the mycotoxin cytochalasin B on induction of cytotoxicity,modulation of cell cycle,Ca²⁺ homeostasis and ROS production in human breast cells[J].Toxicology,2016,370:1-19.
[20] Hu Z,Yang A,Fan H,et al.Huaier aqueous extract sensitizes cells to rapamycin and cisplatin through activating mTOR signaling[J].J Ethnopharmacol,2016,186:143-150.
[21] Lee SH,Kwak CH,Lee SK,et al.Anti-inflammatory effect of ascochlorin in LPS-stimulated RAW 264.7 macrophage cells is accompanied with the down-regulation of iNOS,COX-2 and proinflammatory cytokines through NF-kappaB,ERK1/2,and p38 signaling pathway[J].J Cell Biochem,2016,117(4):978-987.
[22] Bhatia DR,Dhar P,Mutalik V,et al.Anticancer activity of Ophiobolin A,isolated from the endophytic fungus bipolaris setariae[J].Nat Prod Res,2016,30(12):1455-1458.
[23] Tian X,Li Y,Shen Y,et al.Apoptosis and inhibition of proliferation of cancer cells induced by cordycepin[J].Oncol Lett,2015,10(2):595-599.
[24] Yokoigawa J,Morimoto K,Shiono Y,et al.Allantopyrone A,an alpha-pyrone metabolite from an endophytic fungus,inhibits the tumor necrosis factor alpha-induced nuclear factor kappa B signaling pathway[J].J Antibiot(Tokyo),2015,68(2):71-75.
[25] Wang Y,Qi X,Li D,et al.Anticancer efficacy and absorption,distribution,metabolism,and toxicity studies of aspergiolide A in early drug development[J].Drug Des Devel Ther,2014,8:1965-1977.
[26] Kundu S,Kim TH,Yoon JH,et al.Viriditoxin regulates apoptosis and autophagy via mitotic catastrophe and microtubule formation in human prostate cancer cells[J].Int J Oncol,2014,45(6):2331-2340.
[27] Song Y,Dou H,Wang P,et al.A novel small-molecule compound diaporine A inhibits non-small cell lung cancer growth by regulating miR-99a/mTOR signaling[J].Cancer Biol Ther,2014,15(10):1423-1430.
[28] Li YX,Kang KH,Kim HJ,et al.In vitro induction of apoptosis by isosclerone from marine-derived fungus Aspergillus fumigatus[J].Bioorg Med Chem Lett,2014,24(16):3923-3927.
[29] Hsiao CJ,Hsiao G,Chen WL,et al.Cephalochromin induces G0/G1 cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by inflicting mitochondrial disruption[J].J Nat Prod,2014,77(4):758-765.
[30] Kim KS,Cui X,Lee DS,et al.Inhibitory effects of benzaldehyde derivatives from the marine fungus Eurotium sp SF-5989 on inflammatory mediators via the induction of heme oxygenase-1 in lipopolysaccharide-stimulated RAW264.7 macrophages[J].Int J Mol Sci,2014,15(12):23749-23765.
[31] Li YX,Himaya S,Dewapriya P,et al.Anti-proliferative effects of isosclerone isolated from marine fungus Aspergillus fumigatus in MCF-7 human breast cancer cells[J].Process Biochemistry,2014,49(12):2292-2298.
[32] Chen YJ,Thang MW,Chan YT,et al.Global assessment of Antrodia cinnamomea-induced microRNA alterations in hepatocarcinoma cells[J].PLoS One,2013,8(12):e82751.
[33] Li YX,Himaya SW,Dewapriya P,et al.Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells[J].Mar Drugs,2013,11(12):5063-5086.
[34] Su J,Zhao P,Kong L,et al.Trichothecin induces cell death in NF-kappaB constitutively activated human cancer cells via inhibition of IKKbeta phosphorylation[J].PLoS One,2013,8(8):e71333.
[35] Palanivel K,Kanimozhi V,Kadalmani B,et al.Verrucarin A,a protein synthesis inhibitor,induces growth inhibition and apoptosis in breast cancer cell lines MDA-MB-231 and T47D[J].Biotechnol Lett,2013,35(9):1395-1403.
[36] Kuo HP,Hsu SC,Ou CC,et al.Ganoderma tsugae extract inhibits growth of HER2-Overexpressing cancer cells via Modulation of HER2/PI3K/Akt Signaling Pathway[J].Evid Based Complement Alternat Med,2013,2013:219472.
[37] Yang HL,Lin KY,Juan YC,et al.The anti-cancer activity of Antrodia camphorata against human ovarian carcinoma (SKOV-3) cells via modulation of HER-2/neu signaling pathway[J].J Ethnopharmacol,2013,148(1):254-265.
[38] Xia XC,Chen Q,Liu K,et al.Mycoepoxydiene inhibits antigen-stimulated activation of mast cells and suppresses IgE-mediated anaphylaxis in mice[J].Int Immunopharmacol,2013,17(2):336-341.
[39] Chen Q,Chen T,Li W,et al.Mycoepoxydiene inhibits lipopolysaccharide-induced inflammatory responses through the suppression of TRAF6 polyubiquitination[J].PLoS One,2012,7(9):e44890.
[40] Cao S,Cryan L,Habeshian KA,et al.Phenolic compounds as antiangiogenic CMG2 inhibitors from Costa rican endophytic fungi[J].Bioorg Med Chem Lett,2012,22(18):5885-5888.
[41] Jeong JH,Jeong YJ,Cho HJ,et al.Ascochlorin inhibits growth factor-induced HIF-1alpha activation and tumor-angiogenesis through the suppression of EGFR/ERK/p70S6K signaling pathway in human cervical carcinoma cells[J].J Cell Biochem,2012,113(4):1302-1313.
[42] Ma B,Hottiger MO.Crosstalk between Wnt/beta-Catenin and NF-kappaB signaling pathway during inflammation[J].Front Immunol,2016,7:378.
[43] Chen H,Yang X,Feng Z,et al.Prognostic value of Caspase-3 expression in cancers of digestive tract:a meta-analysis and systematic review[J].Int J Clin Exp Med,2015,8(7):10225-10234.
[44] Chen Y,Zhang H,Zhou HJ,et al.Mitochondrial redox signaling and tumor progression[J].Cancers (Basel),2016,8(4).
[45] Rauch N,Rukhlenko OS,Kolch W,et al.MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance[J].Curr Opin Struct Biol,2016,41:151-158.
[46] Varinska L,Gal P,Mojzisova G,et al.Soy and breast cancer:focus on angiogenesis[J].Int J Mol Sci,2015,16(5):11728-11749.
[47] Lee HH,Kim SO,Kim GY,et al.Involvement of autophagy in cordycepin-induced apoptosis in human prostate carcinoma LNCaP cells[J].Environ Toxicol Pharmacol,2014,38(1):239-250.
[48] Darsih C,Prachyawarakorn V,Wiyakrutta S,et al.Cytotoxic metabolites from the endophytic fungus Penicillium chermesinum:discovery of a cysteine-targeted Michael acceptor as a pharmacophore for fragment-based drug discovery,bioconjugation and click reactions[J].Rsc Advances,2015,5(86):70595-70603.
[49] Ramos AA,Prata-Sena M,Castro-Carvalho B,et al.Potential of four marine-derived fungi extracts as anti-proliferative and cell death-inducing agents in seven human cancer cell lines[J].Asian Pac J Trop Med,2015,8(10):782-790.
[50] Gill BS,Kumar S,Navgeet.Triterpenes in cancer:significance and their influence[J].Mol Biol Rep,2016,43(9):881-896.