Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells

Cancer Letters

Volumn 354, Issue 2, 2014, Pages 407-416

  Peng, Meiyu ^a,b   Huang, Bingqing ^a   Zhang, Qi ^a   Fu, Shuyu ^a   Wang, Dan ^a   Cheng, Xixi ^a   Wu, Xi ^a   Xue, Zhenyi ^a   Zhang, Lijuan ^a   Zhang, Da ^a   Da, Yurong ^a   Dai, Yun ^c   Yang, Qing ^a   Yao, Zhi ^a   Qiao, Liang ^d   Zhang, Rongxin ^a  

^a TIANJIN MEDICAL UNIVERSITY   (China)

^b WEIFANG MEDICAL UNIVERSITY   (China)

^c PEKING UNIVERSITY FIRST HOSPITAL   (China)

^d UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Embelin; IL 6; Inflammation; MDSCs; Pancreatic cancer

Indexed keywords

EMBELIN; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 17; INTERLEUKIN 6; PROTEIN P53; STAT3 PROTEIN; BENZOQUINONE DERIVATIVE; STAT3 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER INHIBITION; CARCINOGENICITY; CELL INFILTRATION; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; CYTOTOXICITY; DOWN REGULATION; FEMALE; GM CSF+ T HELPER CELL; IL 17A+ TH17 CELL; IMMUNOCOMPETENT CELL; IN VIVO STUDY; INFLAMMATORY CELL; LYMPHOCYTIC INFILTRATION; MOUSE; MYELOID DERIVED SUPPRESSOR CELL; NONHUMAN; PANCREAS CANCER; PROTEIN PHOSPHORYLATION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; TH1 CELL; TH17 CELL; TH2 CELL; ANIMAL; C57BL MOUSE; CELL MOTION; DISEASE COURSE; DISEASE MODEL; DRUG EFFECTS; IMMUNOLOGY; INFLAMMATION; METABOLISM; PANCREATIC NEOPLASMS; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; APOPTOSIS; BENZOQUINONES; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DOWN-REGULATION; FEMALE; INFLAMMATION; INTERLEUKIN-6; MICE; MICE, INBRED C57BL; PANCREATIC NEOPLASMS; STAT3 TRANSCRIPTION FACTOR; T-LYMPHOCYTES, REGULATORY; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84908003355     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2014.08.011     Document Type: Article

References (30)

1. Almhanna K., Philip P.A. Defining new paradigms for the treatment of pancreatic cancer. Curr. Treat. Options Oncol 2011, 12:111-125.
2. Chew V., Toh H.C., Abastado J.-P. Immune microenvironment in tumor progression: characteristics and challenges for therapy. J. Oncol 2012, 2012. 608406.
3. Allensworth J.L., Aird K.M., Aldrich A.J., Batinic-Haberle I., Devi G.R. XIAP inhibition and generation of reactive oxygen species enhances TRAIL sensitivity in inflammatory breast cancer cells. Mol. Cancer Ther 2012, 11:1518-1527.
4. Kalyan Kumar G., Dhamotharan R., Kulkarni N.M., Mahat M.Y., Gunasekaran J., Ashfaque M. Embelin reduces cutaneous TNF-alpha level and ameliorates skin edema in acute and chronic model of skin inflammation in mice. Eur. J. Pharmacol 2011, 662:63-69.
5. Nikolovska-Coleska Z., Xu L., Hu Z., Tomita Y., Li P., Roller P.P., et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. J. Med. Chem 2004, 47:2430-2440.
6. Reuter S., Prasad S., Phromnoi K., Kannappan R., Yadav V.R., Aggarwal B.B. Embelin suppresses osteoclastogenesis induced by receptor activator of NF-kappaB ligand and tumor cells in vitro through inhibition of the NF-kappaB cell signaling pathway. Mol. Cancer Res 2010, 8:1425-1436.
7. Mori T., Doi R., Kida A., Nagai K., Kami K., Ito D., et al. Effect of the XIAP inhibitor Embelin on TRAIL-induced apoptosis of pancreatic cancer cells. J. Surg. Res 2007, 142:281-286.
8. Heo J.Y., Kim H.J., Kim S.M., Park K.R., Park S.Y., Kim S.W., et al. Embelin suppresses STAT3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase PTEN. Cancer Lett 2011, 308:71-80.
9. Kim S.W., Kim S.M., Bae H., Nam D., Lee J.H., Lee S.G., et al. Embelin inhibits growth and induces apoptosis through the suppression of Akt/mTOR/S6K1 signaling cascades. Prostate 2012, 73:296-305.
10. Dai Y., Qiao L., Chan K.W., Yang M., Ye J., Ma J., et al. Peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of Embelin on colon carcinogenesis. Cancer Res 2009, 69:4776-4783.
11. Xue Z., Ge Z., Zhang K., Sun R., Yang J., Han R., et al. Embelin suppresses dendritic cell functions and limits autoimmune encephalomyelitis through the TGF-beta/beta-catenin and STAT3 signaling pathways. Mol. Neurobiol 2014, 49:1087-1101.
12. Dai Y., Jiao H., Teng G., Wang W., Zhang R., Wang Y., et al. Embelin reduces colitis-associated tumorigenesis through limiting IL-6/STAT3 signaling. Mol. Cancer Ther 2014, 13:1206-1216.
13. Feurino L.W., Zhang Y., Bharadwaj U., Zhang R., Li F., Fisher W.E., et al. IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells. Cancer Biol. Ther 2007, 6:1096-1100.
14. Oh K., Lee O.Y., Shon S.Y., Nam O., Ryu P.M., Seo M.W., et al. A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model. Breast Cancer Res 2013, 15:R79.
15. Joy B., Sivadasan R., Abraham T.E., John M., Sobhan P.K., Seervi M., et al. Lysosomal destabilization and cathepsin B contributes for cytochrome c release and caspase activation in embelin-induced apoptosis. Mol. Carcinog 2010, 49:324-336.
16. Mantovani A., Allavena P., Sica A., Balkwill F. Cancer-related inflammation. Nature 2008, 454:436-444.
17. Galon J., Costes A., Sanchez-Cabo F., Kirilovsky A., Mlecnik B., Lagorce-Pages C., et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006, 313:1960-1964.
18. Swann J.B., Smyth M.J. Immune surveillance of tumors. J. Clin. Invest 2007, 117:1137-1146.
19. De Monte L., Reni M., Tassi E., Clavenna D., Papa I., Recalde H., et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med 2011, 208:469-478.
20. Peters A., Lee Y., Kuchroo V.K. The many faces of Th17 cells. Curr. Opin. Immunol 2011, 23:702-706.
21. Su X., Ye J., Hsueh E.C., Zhang Y., Hoft D.F., Peng G. Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J. Immunol 2010, 184:1630-1641.
22. Guthrie G.J., Roxburgh C.S., Horgan P.G., McMillan D.C. Does interleukin-6 link explain the link between tumour necrosis, local and systemic inflammatory responses and outcome in patients with colorectal cancer?. Cancer Treat. Rev 2012, 39:89-96.
23. Vasiliades G., Kopanakis N., Vasiloglou M., Zografos G., Margaris H., Masselou K., et al. Role of the hematopoietic cytokines SCF, IL-3, GM-CSF and M-CSF in the diagnosis of pancreatic and ampullary cancer. Int. J. Biol. Markers 2012, 27:e186-e194.
24. Bharadwaj U., Li M., Zhang R., Chen C., Yao Q. Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned medium suppress dendritic cell differentiation and activation. Cancer Res 2007, 67:5479-5488.
25. Grivennikov S.I., Greten F.R., Karin M. Immunity, inflammation, and cancer. Cell 2010, 140:883-899.
26. Ino Y., Yamazaki-Itoh R., Shimada K., Iwasaki M., Kosuge T., Kanai Y., et al. Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br. J. Cancer 2013, 108:914-923.
27. Porembka M.R., Mitchem J.B., Belt B.A., Hsieh C.S., Lee H.M., Herndon J., et al. Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunol. Immunother 2012, 61:1373-1385.
28. Mace T.A., Ameen Z., Collins A., Wojcik S., Mair M., Young G.S., et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner. Cancer Res 2013, 73:3007-3018.
29. Liu A., Liu Y., Li P.K., Li C., Lin J. LLL12 inhibits endogenous and exogenous interleukin-6-induced STAT3 phosphorylation in human pancreatic cancer cells. Anticancer Res 2011, 31:2029-2035.
30. Narayan C., Kumar A. Constitutive over expression of IL-1β, IL-6, NF-κB, and Stat3 is a potential cause of lung tumorgenesis in urethane (ethyl carbamate) induced Balb/c mice. J. Carcinog 2012, 11:9.