Kaempferol Suppresses Transforming Growth Factor-β1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179

Neoplasia (United States)

Volumn 17, Issue 7, 2015, Pages 525-537

  Jo, Eunji ^a   Park, Seong Ji ^a   Choi, Yu Sun ^a   Jeon, Woo Kwang ^a   Kim, Byung Chul ^a  

^a Kangwon National University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

AKT1 PROTEIN; BIOLOGICAL MARKER; GELATINASE A; KAEMPFEROL; NERVE CELL ADHESION MOLECULE; PROTEIN KINASE B; SERINE; SMAD3 PROTEIN; SMAD4 PROTEIN; THREONINE; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; UVOMORULIN; VIMENTIN; AKT1 PROTEIN, HUMAN; ANTINEOPLASTIC AGENT; CADHERIN; DNA BINDING PROTEIN; KAEMPFEROL DERIVATIVE; MMP2 PROTEIN, HUMAN; SMAD3 PROTEIN, HUMAN; SMAD4 PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

A549 CELL LINE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL MIGRATION; COMPLEX FORMATION; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; HUMAN CELL; LUNG CANCER CELL LINE; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN INDUCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; UPREGULATION; ACTIVE TRANSPORT; ANTAGONISTS AND INHIBITORS; CELL MOTION; DRUG EFFECTS; GENETICS; LUNG TUMOR; METABOLISM; NEOPLASM METASTASIS; NON SMALL CELL LUNG CANCER; PATHOLOGY; PHOSPHORYLATION; PROTEIN TRANSPORT; TUMOR CELL LINE;

ACTIVE TRANSPORT, CELL NUCLEUS; ANTINEOPLASTIC AGENTS; CADHERINS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CELL MOVEMENT; DNA-BINDING PROTEINS; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; KAEMPFEROLS; LUNG NEOPLASMS; MATRIX METALLOPROTEINASE 2; NEOPLASM METASTASIS; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; PROTEIN TRANSPORT; PROTO-ONCOGENE PROTEINS C-AKT; SMAD3 PROTEIN; SMAD4 PROTEIN; SNAIL FAMILY TRANSCRIPTION FACTORS; TRANSCRIPTION FACTORS; TRANSFORMING GROWTH FACTOR BETA1;

EID: 84963985160     PISSN: 15228002     EISSN: 14765586     Source Type: Journal    
DOI: 10.1016/j.neo.2015.06.004     Document Type: Article

References (48)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
2. Tsai JH, Yang J Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev 2013, 27:2192-2206.
3. Voulgari A, Pintzas A Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta 2009, 1796:75-90.
4. Bierie B, Moses HL TGF-β and cancer. Cytokine Growth Factor Rev 2006, 17:29-40.
5. Roberts AB, Wakefield LM The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci U S A 2003, 100:8621-8623.
6. Boudreau HE, Casterline BW, Rada B, Korzeniowska A, Leto TL Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells. Free Radic Biol Med 2012, 53:1489-1499.
7. Roberts AB, Tian F, Byfield SD, Stuelten C, Ooshima A, Saika S, Flanders KC Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine Growth Factor Rev 2006, 17:19-27.
8. Saika S, Kono-Saika S, Ohnishi Y, Sato M, Muragaki Y, Ooshima A, Flanders KC, Yoo J, Anzano M, Liu CY, et al. Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. Am J Pathol 2004, 164:651-653.
9. Fuxe J, Vincent T, Garcia de Herreros A Transcriptional crosstalk between TGFβ and stem cell pathways in tumor cell invasion: role of EMT promoting Smad conplexes. Cell Cycle 2010, 9:2363-2374.
10. Hua F, Mu R, Liu J, Xue J, Wang Z, Lin H, Yang H, Chen X, Hu Z TRB3 interacts with SMAD3 promoting tumor cell migration and invasion. J Cell Sci 2011, 124:3235-3246.
11. Xue J, Lin X, Chiu WT, Chen YH, Yu G, Liu M, Feng XH, Sawaya R, Medema RH, Hung MC, et al. Sustained activation of SMAD3/SMAD4 by FOXM1 promotes TGF-β-dependent cancer metastasis. J Clin Invest 2014, 124:564-579.
12. Ahan SM, Cha JY, Kim J, Kim D, Trang HT, Kim YM, Cho YH, Park D, Hong S Smad3 regulates E-cadherin via miRNA-200 pathway. Oncogene 2012, 31:3051-3059.
13. Miyazono K, Suzuki H, Imamura T Regulation of TGF-β signaling and its roles in progression of tumors. Cancer Sci 2003, 94:230-234.
14. Shi Y, Massagué J Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 2003, 113:685-700.
15. Engel ME, McDonnell MA, Law BK, Moses HL Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription. J Biol Chem 1999, 274:37413-37420.
16. Kamaraju AK, Roberts AB Role of Rho/ROCK and p38 MAPK kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. J Biol Chem 2005, 280:1024-1036.
17. Liu F Smad3 phosphorylation by cyclin-dependent kinases. Cytokine Growth Factor Rev 2006, 17:9-17.
18. Millet C, Yamashita M, Heller M, Yu LR, Veenstra TD, Zhang YE A negative feedback control of transforming growth factor-beta signaling by glycogen synthase kinase 3-mediated Smad3 linker phosphorylation at Ser-204. J Biol Chem 2009, 284:19808-19816.
19. Mori S, Matsuzaki K, Yoshida K, Furukawa F, Tahashi Y, Yamagata H, Sekimoto G, Seki T, Matsui H, Nishizawa M, et al. TGF-β and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker region. Oncogene 2004, 23:7416-7429.
20. Murata M, Matsuzaki K, Yoshida K, Sekimoto G, Tahashi Y, Mori S, Uemura Y, Sakaida N, Fujisawa J, Seki T, et al. Hepatatis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta from tumor suppression to oncogenesis in early chronic hepatitis B. Hepatology 2009, 49:1203-1217.
21. Kretzschmar M, Doody J, Timokhina I, Massagué J A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev 1999, 13:804-816.
22. Choi J, Park SJ, Jo EJ, Lee HY, Hong S, Kim SJ, Kim BC Hydrogen peroxide inhibits transforming growth factor-β1-induced cell cycle arrest by promoting Smad3 linker phosphorylation through activation of Akt-ERK1/2-linked signaling pathway. Biochem Biophys Res Commun 2013, 435:634-639.
23. Calderón-Montaño JM, Burgos-Morón E, Pérez-Guerrero C, López-Lázaro M A review on the dietary flavonoid kaempferol. Mini Rev Med Chem 2011, 11:298-344.
24. Cho YY, Yao K, Kim HG, Kang BS, Zheng D, Bode AM, Dong Z Ribosomal S6 kinase 2 is a key regulator in tumor promoter induced cell transformation. Cancer Res 2007, 67:8104-8112.
25. Lee KM, Lee DE, Seo SK, Hwang MK, Heo YS, Lee KW, Lee HJ Phosphatidylinositol 3-kinase, a novel target molecule for the inhibitory effects of kaempferol on neoplastic cell transformation. Carcinogenesis 2010, 31:1338-1343.
26. Smith JA, Maloney DJ, Clark DE, Xu Y, Hecht SM, Lannigan DA Influence of rhamnose substituents on the potency of SL0101, an inhibitor of the Ser/Thr kinase, RSK. Bioorg Med Chem 2006, 14:6034-6042.
27. Xie F, Su M, Qiu W, Zhang M, Guo Z, Su B, Liu J, Li X, Zhou L Kaempferol promotes apoptosis in human bladder cancer cells by inducing the tumor suppressor, PTEN. Int J Mol Sci 2013, 14:21215-21226.
28. Luo H, Rankin GO, Liu L, Daddysman MK, Jiang BH, Chen YC Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells. Nutr Cancer 2009, 61:554-563.
29. Lin CW, Chen PN, Chen MK, Yang WE, Tang CH, Yang SF, Hsieh YS Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells. PLoS One 2013, 8:e80883.
30. Chomczynski P, Sacchi N Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987, 162:575156-575159.
31. Kim AN, Jeon WK, Lim KH, Lee HY, Kim WJ, Kim BC Fyn mediates transforming growth factor-beta1-induced down-regulation of E-cadherin in human A549 lung cancer cells. Biochem Biophys Res Commun 2011, 407:181-184.
32. Duffy MJ, Maguire TM, Hill A, McDermott E, O'Higgins N Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2000, 2:252-257.
33. Runyan CE, Schnaper HW, Poncelet AC The phosphatidylinositol 3-kinase/Akt pathway enhances Smad3-stimulated mesangial cell collagen I expression in response to transforming growth factor-beta1. J Biol Chem 2004, 279:2632-2639.
34. Zhao D, Lu Y, Yang C, Zhou X, Xu Z Activation of FGF receptor signaling promotes invasion of non-small-cell lung cancer. Tumor Biol 2015, 36:3637-3642.
35. Lee CJ, Lee MH, Cho YY Fibroblast and epidermal growth factors utilize different signaling pathways to induce anchorage-independent cell transformation in JB6 Cl41 mouse skin epidermal cells. J Cancer Prev 2014, 19:199-208.
36. Huang JW, Guan BZ, Yin LH, Liu FN, Hu B, Zheng QY, Li FL, Zhong YX, Chen Y Effects of estrogen-related receptor alpha (ERRα) on proliferation and metastasis of human lung cancer A549 cells. J Huazhong Univ Sci Technolog Med Sci 2014, 34:875-881.
37. Wang H, Gao M, Wang J Kaempferol inhibits cancer cell growth by antagonizing estrogen-related receptor α and γ activities. Cell Biol Int 2013, 37:1190-1196.
38. Ashcroft GS, Yang X, Glick AB, Wenstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C, et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1999, 1:260-266.
39. Kretschmer A, Moepert K, Dames S, Stemberger M, Kaufmann J, Klippel A Differential regulation of TGF-beta signaling through Smad2, Smad3 and Smad4. Oncogene 2003, 22:6748-6763.
40. Malhotra N, Robertson E, Kang J SMAD2 is essential for TGF beta-mediated Th17 cell generation. J Biol Chem 2010, 285:29044-29048.
41. Wrighton KH, Willis D, Long J, Liu F, Lin X, Feng XH Small C-terminal domain phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling. J Biol Chem 2006, 281:38365-38375.
42. Sapkota G, Knockaert M, Alarcón C, Montalvo E, Brivanlou AH, Massagué J Dephosphorylation of the linker regions of Smad1 and Smad2/3 by small C-terminal domain phosphatases has distinct outcomes for bone morphogenetic protein and transforming growth factor-beta pathways. J Biol Chem 2006, 281:40412-40419.
43. Matsuura I, Denissova NG, Wang G, He D, Long J, Liu F Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 2004, 430:226-231.
44. Bae E, Sato M, Kim RJ, Kwak MK, Naka K, Gim J, Kadota M, Tang B, Flanders KC, Kim TA, et al. Definition of smad3 phosphorylation events that affect malignant and metastatic behaviors in breast cancer cells. Cancer Res 2014, 74:6139-6149.
45. Nagata H, Hatano E, Tada M, Murata M, Kitamura K, Asechi H, Narita M, Yanagida A, Tamaki N, Yagi S, et al. Inhibition of c-Jun NH2-terminal kinase switches Smad3 signaling from oncogenesis to tumor-suppression in rat hepatocellular carcinoma. Hepatology 2009, 49:1944-1953.
46. Matsuzaki K Smad phosphor-isoforms direct context-dependent TGF-β signaling. Cytokine Growth Factor Rev 2013, 24:385-399.
47. Nguyen TT, Tran E, Ong CK, Lee SK, Do PT, Huynh TT, Nguyen TH, Lee JJ, Tan Y, Ong CS, et al. Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. J Cell Physiol 2003, 197:110-121.
48. Zhang L, Zhou F, ten Dijke P Signaling interplay between transforming growth factor-β receptor and PI3K/AKT pathways in cancer. Trends Biochem Sci 2013, 38:612-620.