Emodin Suppresses Migration and Invasion through the Modulation of CXCR4 Expression in an Orthotopic Model of Human Hepatocellular Carcinoma

PLoS ONE

Volumn 8, Issue 3, 2013, Pages

  Manu, Kanjoormana Aryan ^a   Shanmugam, Muthu K ^a   Ong, Tina H ^b   Subramaniam, Aruljothi ^a,c   Siveen, Kodappully Sivaraman ^a   Perumal, Ekambaram ^c   Samy, Ramar Perumal ^d   Bist, Pradeep ^d   Lim, Lina H K ^d   Kumar, Alan Prem ^a,e,f,g   Hui, Kam M ^b   Sethi, Gautam ^a,d  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b DIVISION OF MEDICAL ONCOLOGY   (Singapore)

^c BHARATHIAR UNIVERSITY   (India)

^d NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^e NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^f CURTIN UNIVERSITY   (Australia)

^g UNIVERSITY OF NORTH TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR CXCR4; EMODIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MESSENGER RNA; CXCR4 PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER INVASION; CELL MIGRATION; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; CORRELATIONAL STUDY; CXCR4 GENE; DOWN REGULATION; DRUG STRUCTURE; DRUG TARGETING; EXPERIMENTAL MOUSE; GENE EXPRESSION REGULATION; GENE FUNCTION; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; LIVER TRANSPLANTATION; LUNG METASTASIS; METASTASIS INHIBITION; MIGRATION INHIBITION; MOUSE; NONHUMAN; PROTEIN DEGRADATION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; ANIMAL; BAGG ALBINO MOUSE; CANCER TRANSPLANTATION; CELL MOTION; DOSE RESPONSE; DRUG EFFECTS; FEMALE; LIVER TUMOR; METABOLISM; REPORTER GENE; SIGNAL TRANSDUCTION; TUMOR CELL LINE; TUMOR INVASION; WOUND HEALING;

ANIMALS; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CELL MOVEMENT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; EMODIN; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, REPORTER; HUMANS; LIVER NEOPLASMS; MICE; MICE, INBRED BALB C; NEOPLASM INVASIVENESS; NEOPLASM TRANSPLANTATION; NF-KAPPA B; RECEPTORS, CXCR4; RNA, MESSENGER; SIGNAL TRANSDUCTION; WOUND HEALING;

EID: 84874638221     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0057015     Document Type: Article

References (36)

1. Lin H, van den Esschert J, Liu C, van Gulik TM, (2011) Systematic review of hepatocellular adenoma in China and other regions. J Gastroenterol Hepatol 26: 28-35.
2. He G, Karin M, (2011) NF-kappaB and STAT3- key players in liver inflammation and cancer. Cell Res 21: 159-168.
3. Nguyen DX, Bos PD, Massague J, (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9: 274-284.
4. Lazennec G, Richmond A, (2010) Chemokines and chemokine receptors: new insights into cancer-related inflammation. Trends Mol Med 16: 133-144.
5. Teicher BA, Fricker SP, (2010) CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res 16: 2927-2931.
6. Liu H, Pan Z, Li A, Fu S, Lei Y, et al. (2008) Roles of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in metastasis of hepatocellular carcinoma cells. Cell Mol Immunol 5: 373-378.
7. Xiang Z, Zeng Z, Tang Z, Fan J, Sun H, et al. (2009) Increased expression of vascular endothelial growth factor-C and nuclear CXCR4 in hepatocellular carcinoma is correlated with lymph node metastasis and poor outcome. Cancer J 15: 519-525.
8. Xiang ZL, Zeng ZC, Tang ZY, Fan J, Zhuang PY, et al. (2009) Chemokine receptor CXCR4 expression in hepatocellular carcinoma patients increases the risk of bone metastases and poor survival. BMC Cancer 9: 176.
9. Huang F, Geng XP, (2010) Chemokines and hepatocellular carcinoma. World J Gastroenterol 16: 1832-1836.
10. Singh S, Singh UP, Grizzle WE, Lillard JW Jr, (2004) CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Lab Invest 84: 1666-1676.
11. Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, et al. (2005) Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 23: 879-894.
12. Vandercappellen J, Van Damme J, Struyf S, (2008) The role of CXC chemokines and their receptors in cancer. Cancer Lett 267: 226-244.
13. Xiang ZL, Zeng ZC, Tang ZY, Fan J, Sun HC, et al. (2010) [Nuclear accumulation of CXCR4 and overexpressions of VEGF-C and CK19 are associated with a higher risk of lymph node metastasis in hepatocellular carcinoma]. Zhonghua Zhong Liu Za Zhi 32: 344-349.
14. Kumar A, Dhawan S, Aggarwal BB, (1998) Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-kappaB activation, IkappaB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells. Oncogene 17: 913-918.
15. Huang Q, Shen HM, Ong CN, (2004) Inhibitory effect of emodin on tumor invasion through suppression of activator protein-1 and nuclear factor-kappaB. Biochem Pharmacol 68: 361-371.
16. Xia QS, Sun RY, Xiu RJ, (2009) [Progress of research on molecular mechanisms in antitumor effect of emodin]. Zhongguo Zhong Xi Yi Jie He Za Zhi 29: 85-88.
17. Lin ML, Lu YC, Chung JG, Wang SG, Lin HT, et al. (2010) Down-regulation of MMP-2 through the p38 MAPK-NF-kappaB-dependent pathway by aloe-emodin leads to inhibition of nasopharyngeal carcinoma cell invasion. Mol Carcinog 49: 783-797.
18. Tabolacci C, Lentini A, Mattioli P, Provenzano B, Oliverio S, et al. (2010) Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16-F10 melanoma cells. Life Sci 87: 316-324.
19. Fernandis AZ, Prasad A, Band H, Klosel R, Ganju RK, (2004) Regulation of CXCR4-mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene 23: 157-167.
20. Bhandari D, Trejo J, Benovic JL, Marchese A, (2007) Arrestin-2 interacts with the ubiquitin-protein isopeptide ligase atrophin-interacting protein 4 and mediates endosomal sorting of the chemokine receptor CXCR4. J Biol Chem 282: 36971-36979.
21. Helbig G, Christopherson KW 2nd, Bhat-Nakshatri P, Kumar S, Kishimoto H, et al (2003) NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem 278: 21631-21638.
22. Nasuhara Y, Adcock IM, Catley M, Barnes PJ, Newton R, (1999) Differential IkappaB kinase activation and IkappaBalpha degradation by interleukin-1beta and tumor necrosis factor-alpha in human U937 monocytic cells. Evidence for additional regulatory steps in kappaB-dependent transcription. J Biol Chem 274: 19965-19972.
23. Proudfoot AE, (2002) Chemokine receptors: multifaceted therapeutic targets. Nat Rev Immunol 2: 106-115.
24. Libura J, Drukala J, Majka M, Tomescu O, Navenot JM, et al. (2002) CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion. Blood 100: 2597-2606.
25. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, et al. (2003) Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425: 307-311.
26. Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, et al. (2003) Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 198: 1391-1402.
27. Bachelder RE, Wendt MA, Mercurio AM, (2002) Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. Cancer Res 62: 7203-7206.
28. Kulbe H, Hagemann T, Szlosarek PW, Balkwill FR, Wilson JL, (2005) The inflammatory cytokine tumor necrosis factor-alpha regulates chemokine receptor expression on ovarian cancer cells. Cancer Res 65: 10355-10362.
29. Benovic JL, Marchese A, (2004) A new key in breast cancer metastasis. Cancer Cell 6: 429-430.
30. Arya M, Ahmed H, Silhi N, Williamson M, Patel HR, (2007) Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration. Tumour Biol 28: 123-131.
31. Subik K, Shu L, Wu C, Liang Q, Hicks D, et al. (2012) The ubiquitin E3 ligase WWP1 decreases CXCL12-mediated MDA231 breast cancer cell migration and bone metastasis. Bone 50: 813-823.
32. Sethi G, Tergaonkar V, (2009) Potential pharmacological control of the NF-kappaB pathway. Trends Pharmacol Sci 30: 313-321.
33. Ok S, Kim SM, Kim C, Nam D, Shim BS, et al. (2012) Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4. Immunopharmacol Immunotoxicol.
34. Li Y, Tang Y, Ye L, Liu B, Liu K, et al. (2003) Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol 129: 43-51.
35. Chua AW, Hay HS, Rajendran P, Shamugam MK, Li F, et al. (2010) Butein Downregulates Chemokine Receptor CXCR4 Expression and Function through suppression of NF-kappaB Activation in Breast and Pancreatic Tumor cells. Biochem Pharmacol.
36. Rajendran P, Ong TH, Chen L, Li F, Shanmugam MK, et al. (2011) Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo. Clin Cancer Res 17: 1425-1439.