Hispidulin, a small flavonoid molecule, suppresses the angiogenesis and growth of human pancreatic cancer by targeting vascular endothelial growth factor receptor 2-mediated PI3K/Akt/mTOR signaling pathway

Cancer Science

Volumn 102, Issue 1, 2011, Pages 219-225

  He, Lijun ^a   Wu, Yuanyuan ^a   Lin, Lei ^a   Wang, Jieqiong ^a   Wu, Yougen ^a   Chen, Yihua ^a   Yi, Zhengfang ^a   Liu, Mingyao ^a,b   Pang, Xiufeng ^a  

^a EAST CHINA NORMAL UNIVERSITY   (China)

^b TEXAS A AND M HEALTH SCIENCE CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FOCAL ADHESION KINASE; HISPIDULIN; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN S6; VASCULOTROPIN RECEPTOR 2;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIANGIOGENIC ACTIVITY; ARTICLE; CANCER INHIBITION; CELL INVASION; CELL MIGRATION; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; DRUG SENSITIVITY; DRUG TARGETING; ENDOTHELIUM CELL; HUMAN; HUMAN CELL; IN VITRO STUDY; MOUSE; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR GROWTH;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE; CELL MOVEMENT; CORNEAL NEOVASCULARIZATION; ENDOTHELIAL CELLS; FLAVONES; HUMANS; MALE; MICE; MICE, INBRED BALB C; PANCREATIC NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RATS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 78650207710     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2010.01778.x     Document Type: Article

References (38)

1. Jemal A, Clegg LX, Ward E et al. Annual report to the nation on the status of cancer, 1975-2001, with a special feature regarding survival. Cancer 2004; 101: 3-27.
2. Solorzano CC, Baker CH, Bruns CJ et al. Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Cancer Biother Radiopharm 2001; 16: 359-70.
3. Abdelrahim M, Konduri S, Basha R, Philip PA, Baker CH. Angiogenesis: an update and potential drug approaches (review). Int J Oncol 2010; 36: 5-18.
4. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003; 3: 401-10.
5. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23: 1011-27.
6. McMahon G. VEGF receptor signaling in tumor angiogenesis. Oncologist 2000; 5 (Suppl 1): 3-10.
7. Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res 2006; 12: 5018-22.
8. Shiojima I, Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ Res 2002; 90: 1243-50.
9. Cho DH, Choi YJ, Jo SA et al. Troglitazone acutely inhibits protein synthesis in endothelial cells via a novel mechanism involving protein phosphatase 2A-dependent p70 S6 kinase inhibition. Am J Physiol Cell Physiol 2006; 291: C317-26.
10. Foster KG, Acosta-Jaquez HA, Romeo Y et al. Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation. J Biol Chem 2010; 285: 80-94.
11. Hwang M, Perez CA, Moretti L, Lu B. The mTOR signaling network: insights from its role during embryonic development. Curr Med Chem 2008; 15: 1192-208.
12. Lee DF, Kuo HP, Chen CT et al. IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell 2007; 130: 440-55.
13. Mahalingam D, Sankhala K, Mita A, Giles FJ, Mita MM. Targeting the mTOR pathway using deforolimus in cancer therapy. Future Oncol 2009; 5: 291-303.
14. O'Reilly KE, Rojo F, She QB et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006; 66: 1500-8.
15. Ghayad SE, Cohen PA. Inhibitors of the PI3K/Akt/mTOR pathway: new hope for breast cancer patients. Recent Pat Anticancer Drug Discov 2010; 5: 29-57.
16. Lopez-Fauqued M, Gil R, Grueso J et al. The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. Int J Cancer 2010; 126: 1549-61.
17. Yin Y, Gong FY, Wu XX et al. Anti-inflammatory and immunosuppressive effect of flavones isolated from Artemisia vestita. J Ethnopharmacol 2008; 120: 1-6.
18. Shen XL, Nielsen M, Witt MR, Sterner O, Bergendorff O, Khayyal M. Inhibition of [methyl-3H]diazepam binding to rat brain membranes in vitro by dinatin and skrofulein. Zhongguo Yao Li Xue Bao 1994; 15: 385-8.
19. Kavvadias D, Monschein V, Sand P, Riederer P, Schreier P. Constituents of sage (Salvia officinalis) with in vitro affinity to human brain benzodiazepine receptor. Planta Med 2003; 69: 113-7.
20. Kavvadias D, Sand P, Youdim KA et al. The flavone hispidulin, a benzodiazepine receptor ligand with positive allosteric properties, traverses the blood-brain barrier and exhibits anticonvulsive effects. Br J Pharmacol 2004; 142: 811-20.
21. Tan RX, Lu H, Wolfender JL et al. Mono- and sesquiterpenes and antifungal constituents from Artemisia species. Planta Med 1999; 65: 64-7.
22. Nagao T, Abe F, Kinjo J, Okabe H. Antiproliferative constituents in plants 10. Flavones from the leaves of Lantana montevidensis Briq. and consideration of structure-activity relationship. Biol Pharm Bull 2002; 25: 875-9.
23. Chen YT, Zheng RL, Jia ZJ, Ju Y. Flavonoids as superoxide scavengers and antioxidants. Free Radic Biol Med 1990; 9: 19-21.
24. Bourdillat B, Delautier D, Labat C, Benveniste J, Potier P, Brink C. Mechanism of action of hispidulin, a natural flavone, on human platelets. Prog Clin Biol Res 1988; 280: 211-4.
25. Lin YC, Hung CM, Tsai JC et al. Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK). J Agric Food Chem 2010; 58: 9511-7.
26. Yang JM, Hung CM, Fu CN et al. Hispidulin sensitizes human ovarian cancer cells to TRAIL-induced apoptosis by AMPK activation leading to Mcl-1 block in translation. J Agric Food Chem 2010; 58: 10020-6.
27. Yi T, Yi Z, Cho SG et al. Gambogic acid inhibits angiogenesis and prostate tumor growth by suppressing vascular endothelial growth factor receptor 2 signaling. Cancer Res 2008; 68: 1843-50.
28. Pang X, Yi Z, Zhang X et al. Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Res 2009; 69: 5893-900.
29. Berger AC, Wang XQ, Zalatoris A, Cenna J, Watson JC. A murine model of ex vivo angiogenesis using aortic disks grown in fibrin clot. Microvasc Res 2004; 68: 179-87.
30. Ziche M, Morbidelli L. The corneal pocket assay. Methods Mol Biol 2009; 467: 319-29.
31. Cao Y. Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal 2009; 2: re1.
32. Kraiss LW, Weyrich AS, Alto NM et al. Fluid flow activates a regulator of translation, p70/p85 S6 kinase, in human endothelial cells. Am J Physiol Heart Circ Physiol 2000; 278: H1537-44.
33. Weyrich AS, Denis MM, Schwertz H et al. mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Blood 2007; 109: 1975-83.
34. Maya-Monteiro CM, Almeida PE, D'Avila H et al. Leptin induces macrophage lipid body formation by a phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent mechanism. J Biol Chem 2008; 283: 2203-10.
35. Datta SR, Dudek H, Tao X et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997; 91: 231-41.
36. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 1997; 278: 687-9.
37. Deeb D, Jiang H, Gao X et al. Curcumin [1, 7-bis(4-hydroxy-3-methoxyphenyl)-1-6-heptadine- 3, 5-dione; C21H20O6] sensitizes human prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand/Apo2L-induced apoptosis by suppressing nuclear factor-kappaB via inhibition of the prosurvival Akt signaling pathway. J Pharmacol Exp Ther 2007; 321: 616-25.
38. Liu LZ, Zheng JZ, Wang XR, Jiang BH. Endothelial p70 S6 kinase 1 in regulating tumor angiogenesis. Cancer Res 2008; 68: 8183-8.