期刊论文详细信息
BMC Complementary and Alternative Medicine
Database screening of herbal monomers regulating autophagy by constructing a
Weihui Zhang1  Dongbo Xue1  Xin Qiao2  Xianzhi Meng1  Ming Lu2  Bo Gao1  Zhengpeng Yang1  Chenjun Hao1 
[1] Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China;Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
关键词: Bioinformatics;    Genomics;    Autophagy;    Herbal monomer;   
Others  :  1088421
DOI  :  10.1186/1472-6882-14-466
 received in 2014-07-06, accepted in 2014-11-27,  发布年份 2014
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【 摘 要 】

Background

Studies suggest an important role of autophagy as a target for cancer therapy. We constructed a "disease-gene-drug" network using the modular approach of bioinformatics and screened herbal monomers demonstrating functions related to autophagy regulation.

Methods

Based on the microarray results of the gene expression omnibus (GEO) database (GSE2435 and GSE31040, starvation-induced autophagy model), we used the human protein reference database (HPRD) to obtain the protein-protein interaction (PPI) network. In addition, we used the CFinder software to identify several functional modules, performed gene ontology-biological process (GO-BP) functional enrichment analysis using the DAVID software, constructed a herbal monomer-module gene regulatory network using literature search and the Cytoscape software, and then analyzed the relationships between autophagy, genes, and herbal monomers.

Results

We screened 544 differentially expressed genes related to autophagy, 375 pairs of differentially expressed genes, and 7 gene modules, wherein the functions of module 3 (composed of 7 genes) were enriched in "cell death". Using the constructed herbal monomer-module gene regulatory network, we found that 30 herbal monomers can simultaneously regulate these 7 genes, indicating a potential regulatory role in autophagy.

Conclusions

Database screening using the disease-gene-drug network can provide new strategies and ideas for the application of herbal medicines in cancer therapy.

【 授权许可】

   
2014 Hao et al.; licensee BioMed Central.

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【 参考文献 】
  • [1]Fitzpatrick FA, Wheeler R: The immunopharmacology of paclitaxel (Taxol), docetaxel (Taxotere), and related agents. Int Immunopharmacol 2003, 3:1699-1714.
  • [2]Rates SM: Plants as source of drugs. Toxicon 2001, 39:603-613.
  • [3]Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, Mukherjee C, Shi Y, Gélinas C, Fan Y, Nelson DA, Jin S, White E: Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006, 10:51-64.
  • [4]Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, Cattoretti G, Levine B: Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003, 112:1809-1820.
  • [5]Tsujimoto Y, Shimizu S: Another way to die: autophagic programmed cell death. Cell Death Differ 2005, 12(Suppl 2):1528-1534.
  • [6]Ryter SW, Mizumura K, Choi AM: The impact of autophagy on cell death modalities. Int J Cell Biol 2014, 2014:502676.
  • [7]Altman BJ, Rathmell JC: Metabolic stress in autophagy and cell death pathways. Cold Spring Harb Perspect Biol 2012, 4:a008763.
  • [8]Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, Ahn HJ, Ait-Mohamed O, Ait-Si-Ali S, Akematsu T, Akira S, Al-Younes HM, Al-Zeer MA, Albert ML, Albin RL, Alegre-Abarrategui J, Aleo MF, Alirezaei M, Almasan A, Almonte-Becerril M, Amano A, Amaravadi R, Amarnath S, Amer AO, Andrieu-Abadie N, Anantharam V, et al.: Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012, 8:445-544.
  • [9]Su M, Mei Y, Sinha S: Role of the crosstalk between autophagy and apoptosis in cancer. J Oncol 2013, 2013:102735.
  • [10]Gordy C, He YW: The crosstalk between autophagy and apoptosis: where does this lead? Protein Cell 2012, 3:17-27.
  • [11]Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, Müller M, Kreymborg K, Altenberend F, Brandenburg J, Kalbacher H, Brock R, Driessen C, Rammensee HG, Stevanovic S: Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci U S A 2005, 102:7922-7927.
  • [12]Matarrese P, Tinari A, Ascione B, Gambardella L, Remondini D, Salvioli S, Tenedini E, Tagliafico E, Franceschi C, Malorni W: Survival features of EBV-stabilized cells from centenarians: morpho-functional and transcriptomic analyses. Age (Dordr) 2012, 34:1341-1359.
  • [13]Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, Balakrishnan L, Marimuthu A, Banerjee S, Somanathan DS, Sebastian A, Rani S, Ray S, Harrys Kishore CJ, Kanth S, Ahmed M, Kashyap MK, Mohmood R, Ramachandra YL, Krishna V, Rahiman BA, Mohan S, Ranganathan P, Ramabadran S, Chaerkady R, Pandey A: Human protein reference database–2009 update. Nucleic Acids Res 2009, 37:D767-772.
  • [14]Adamcsek B, Palla G, Farkas IJ, Derenyi I, Vicsek T: CFinder: locating cliques and overlapping modules in biological networks. Bioinformatics 2006, 22:1021-1023.
  • [15]Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T: Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011, 27:431-432.
  • [16]Yang S, Kimmelman AC: A critical role for autophagy in pancreatic cancer. Autophagy 2011, 7:912-913.
  • [17]Toth S, Nagy K, Palfia Z, Rez G: Cellular autophagic capacity changes during azaserine-induced tumour progression in the rat pancreas. Up-regulation in all premalignant stages and down-regulation with loss of cycloheximide sensitivity of segregation along with malignant transformation. Cell Tissue Res 2002, 309:409-416.
  • [18]Hait WN, Jin S, Yang JM: A matter of life or death (or both): understanding autophagy in cancer. Clin Cancer Res 2006, 12:1961-1965.
  • [19]Bursch W, Ellinger A, Kienzl H, Torok L, Pandey S, Sikorska M, Walker R, Hermann RS: Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis 1996, 17:1595-1607.
  • [20]Qian W, Liu J, Jin J, Ni W, Xu W: Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via up-regulation of Beclin-1. Leuk Res 2007, 31:329-339.
  • [21]Kim KW, Mutter RW, Cao C, Albert JM, Freeman M, Hallahan DE, Lu B: Autophagy for cancer therapy through inhibition of pro-apoptotic proteins and mammalian target of rapamycin signaling. J Biol Chem 2006, 281:36883-36890.
  • [22]Liu X, Yu H, Yang W, Zhou X, Lu H, Shi D: Mutations of NFKBIA in biopsy specimens from Hodgkin lymphoma. Cancer Genet Cytogenet 2010, 197:152-157.
  • [23]Yang S, Bing M, Chen F, Sun Y, Chen H, Chen W: Autophagy regulation by the nuclear factor kappaB signal axis in acute pancreatitis. Pancreas 2012, 41:367-373.
  • [24]Gao J, Pfeifer D, He LJ, Qiao F, Zhang Z, Arbman G, Wang ZL, Jia CR, Carstensen J, Sun XF: Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol 2007, 42:345-350.
  • [25]Rinkenbaugh AL, Baldwin AS: Monoallelic deletion of NFKBIA in glioblastoma: when less is more. Cancer Cell 2011, 19:163-165.
  • [26]Tamura RE, de Vasconcellos JF, Sarkar D, Libermann TA, Fisher PB, Zerbini LF: GADD45 proteins: central players in tumorigenesis. Curr Mol Med 2012, 12:634-651.
  • [27]Corcelle E, Djerbi N, Mari M, Nebout M, Fiorini C, Fénichel P, Hofman P, Poujeol P, Mograbi B: Control of the autophagy maturation step by the MAPK ERK and p38: lessons from environmental carcinogens. Autophagy 2007, 3:57-59.
  • [28]Zhang Y, Wu Y, Cheng Y, Zhao Z, Tashiro S, Onodera S, Ikejima T: Fas-mediated autophagy requires JNK activation in HeLa cells. Biochem Biophys Res Commun 2008, 377:1205-1210.
  • [29]Gartel AL, Tyner AL: The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther 2002, 1:639-649.
  • [30]Fujiwara K, Daido S, Yamamoto A, Kobayashi R, Yokoyama T, Aoki H, Iwado E, Shinojima N, Kondo Y, Kondo S: Pivotal role of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in apoptosis and autophagy. J Biol Chem 2008, 283:388-397.
  • [31]Dunlop MG, Dobbins SE, Farrington SM, Jones AM, Palles C, Whiffin N, Tenesa A, Spain S, Broderick P, Ooi LY, Domingo E, Smillie C, Henrion M, Frampton M, Martin L, Grimes G, Gorman M, Semple C, Ma YP, Barclay E, Prendergast J, Cazier JB, Olver B, Penegar S, Lubbe S, Chander I, Carvajal-Carmona LG, Ballereau S, Lloyd A, Vijayakrishnan J, et al.: Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nat Genet 2012, 44:770-776.
  • [32]Kibel AS, Suarez BK, Belani J, Oh J, Webster R, Brophy-Ebbers M, Guo C, Catalona WJ, Picus J, Goodfellow PJ: CDKN1A and CDKN1B polymorphisms and risk of advanced prostate carcinoma. Cancer Res 2003, 63:2033-2036.
  • [33]Chimento SM, Kirsner RS: Understanding the role of c-Jun and Jun B transcription factors in skin cancer developments. J Invest Dermatol 2011, 131:1002.
  • [34]Langer S, Singer CF, Hudelist G, Dampier B, Kaserer K, Vinatzer U, Pehamberger H, Zielinski C, Kubista E, Schreibner M: Jun and Fos family protein expression in human breast cancer: correlation of protein expression and clinicopathological parameters. Eur J Gynaecol Oncol 2006, 27:345-352.
  • [35]Guo Y, Chang C, Huang R, Liu B, Bao L, Liu W: AP1 is essential for generation of autophagosomes from the trans-Golgi network. J Cell Sci 2012, 125:1706-1715.
  • [36]Kojima E, Takeuchi A, Haneda M, Yagi A, Hasegawa T, Yamaki K, Takeda K, Akira S, Shimokata K, Isobe K: The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress: elucidation by GADD34-deficient mice. FASEB J 2003, 17:1573-1575.
  • [37]Talloczy Z, Jiang W, Virgin HWT, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B: Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc Natl Acad Sci U S A 2002, 99:190-195.
  • [38]Liu Y, Laszlo C, Liu Y, Liu W, Chen X, Evans SC, Wu S: Regulation of G(1) arrest and apoptosis in hypoxia by PERK and GCN2-mediated eIF2alpha phosphorylation. Neoplasia 2010, 12:61-68.
  • [39]Filippi-Chiela EC, Thome MP, Silva MM B e, Pelegrini AL, Ledur PF, Garicochea B, Zamin LL, Lenz G: Resveratrol abrogates the temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the temozolomide-induced senescence in glioma cells. BMC Cancer 2013, 13:147. BioMed Central Full Text
  • [40]Lin HY, Tang HY, Keating T, Wu YH, Shih A, Hammond D, Sun M, Hercbergs A, Davis FB, Davis PJ: Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated. Carcinogenesis 2008, 29:62-69.
  • [41]Yamamoto M, Suzuki SO, Himeno M: Resveratrol-induced autophagy in human U373 glioma cells. Oncol Lett 2010, 1:489-493.
  • [42]Choi MS, Kim Y, Jung JY, Yang SH, Lee TR, Shin DW: Resveratrol induces autophagy through death-associated protein kinase 1 (DAPK1) in human dermal fibroblasts under normal culture conditions. Exp Dermatol 2013, 22:491-494.
  • [43]Delmas D, Solary E, Latruffe N: Resveratrol, a phytochemical inducer of multiple cell death pathways: apoptosis, autophagy and mitotic catastrophe. Curr Med Chem 2011, 18:1100-1121.
  • [44]Opipari AW Jr, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR: Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res 2004, 64:696-703.
  • [45]Kueck A, Opipari AW Jr, Griffith KA, Tan L, Choi M, Huang J, Wahl H, Liu JR: Resveratrol inhibits glucose metabolism in human ovarian cancer cells. Gynecol Oncol 2007, 107:450-457.
  • [46]Trincheri NF, Follo C, Nicotra G, Peracchio C, Castino R, Isidoro C: Resveratrol-induced apoptosis depends on the lipid kinase activity of Vps34 and on the formation of autophagolysosomes. Carcinogenesis 2008, 29:381-389.
  • [47]Signorelli P, Munoz-Olaya JM, Gagliostro V, Casas J, Ghidoni R, Fabriàs G: Dihydroceramide intracellular increase in response to resveratrol treatment mediates autophagy in gastric cancer cells. Cancer Lett 2009, 282:238-243.
  • [48]Ohshiro K, Rayala SK, El-Naggar AK, Kumar R: Delivery of cytoplasmic proteins to autophagosomes. Autophagy 2008, 4:104-106.
  • [49]Ohshiro K, Rayala SK, Kondo S, Gaur A, Vadlamudi RK, El-Naggar AK, Kumar R: Identifying the estrogen receptor coactivator PELP1 in autophagosomes. Cancer Res 2007, 67:8164-8171.
  • [50]Puissant A, Robert G, Fenouille N, Luciano F, Cassuto JP, Raynaud S, Auberger P: Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res 2010, 70:1042-1052.
  • [51]Palipoch S, Punsawad C, Koomhin P, Suwannalert P: Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress. BMC Complement Altern Med 2014, 14:111. BioMed Central Full Text
  • [52]El-Bahr SM: Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats. BMC Complement Altern Med 2013, 13:368. BioMed Central Full Text
  • [53]Aoki H, Takada Y, Kondo S, Sawaya R, Aggarwal BB, Kondo Y: Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol Pharmacol 2007, 72:29-39.
  • [54]Kim JY, Cho TJ, Woo BH, Choi KU, Lee CH, Ryu MH, Park HR: Curcumin-induced autophagy contributes to the decreased survival of oral cancer cells. Arch Oral Biol 2012, 57:1018-1025.
  • [55]Li B, Takeda T, Tsuiji K, Wong TF, Tadakawa M, Kondo A, Nagase S, Yaegashi N: Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells. Int J Gynecol Cancer 2013, 23:803-808.
  • [56]Yamauchi Y, Izumi Y, Asakura K, Hayashi Y, Nomori H: Curcumin induces autophagy in ACC-MESO-1 cells. Phytother Res 2012, 26:1779-1783.
  • [57]Han J, Pan XY, Xu Y, Xiao Y, An Y, Tie L, Pan Y, Li XJ: Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage. Autophagy 2012, 8:812-825.
  • [58]Wang K, Liu R, Li J, Mao J, Lei Y, Wu J, Zeng J, Zhang T, Wu H, Chen L, Huang C, Wei Y: Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR- and hypoxia-induced factor 1alpha-mediated signaling. Autophagy 2011, 7:966-978.
  • [59]Kim H, Moon JY, Ahn KS, Cho SK: Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells. Oxid Med Cell Longev 2013, 2013:596496.
  • [60]Choi SI, Kim KS, Oh JY, Jin JY, Lee GH, Kim EK: Melatonin induces autophagy via an mTOR-dependent pathway and enhances clearance of mutant-TGFBIp. J Pineal Res 2013, 54:361-372.
  • [61]Guo Y, Wang J, Wang Z, Yang Y, Wang X, Duan Q: Melatonin protects N2a against ischemia/reperfusion injury through autophagy enhancement. J Huazhong Univ Sci Technolog Med Sci 2010, 30:1-7.
  • [62]Chen J, Wang L, Wu C, Hu Q, Gu C, Yan F, Li J, Yan W, Chen G: Melatonin-enhanced autophagy protects against neural apoptosis via a mitochondrial pathway in early brain injury following a subarachnoid hemorrhage. J Pineal Res 2014, 56:12-19.
  • [63]Niel E, Scherrmann JM: Colchicine today. Joint Bone Spine 2006, 73:672-678.
  • [64]Chen XM, Liu J, Wang T, Shang J: Colchicine-induced apoptosis in human normal liver L-02 cells by mitochondrial mediated pathways. Toxicol In Vitro 2012, 26:649-655.
  • [65]Saxena N, Ansari KM, Kumar R, Dhawan A, Dwivedi PD, Das M: Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p(53) and p(21/WAF1) proteins in skin of mice. Toxicol Appl Pharmacol 2009, 234:192-201.
  • [66]Kwon O, Soung NK, Thimmegowda NR, Jeong SJ, Jang JH, Moon DO, Chung JK, Lee KS, Kwon YT, Erikson RL, Ahn JS, Kim BY: Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation. Cell Signal 2012, 24:943-950.
  • [67]Zhang X, Sheng J, Zhang C, Zhao F: Taurine induces apoptosis in pulmonary artery smooth muscle cells. Zhongguo Zhong Yao Za Zhi 2012, 37:654-657.
  • [68]Shu XL, Xu H, Yu TT, Zhong JX, Lei T: Regulation of apoptosis in human gastric cancer cell line SGC-7901 by L-arginine. Panminerva Med 2014, 56:227-231.
  • [69]Xia J, Duan Q, Ahmad A, Bao B, Banerjee S, Shi Y, Ma J, Geng J, Chen Z, Rahman KM, Miele L, Sarkar FH, Wang Z: Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells. Curr Drug Targets 2012, 13:1750-1756.
  • [70]Kayisli UA, Guzeloglu-Kayisli O, Guzel E, Arici A: Genistein inhibits cell proliferation and stimulates apoptosis in human coronary artery endothelial cells. Gynecol Obstet Invest 2013, 75:235-242.
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