Saponins from the Roots of Platycodon grandiflorum Suppresses TGFβ1-Induced Epithelial-Mesenchymal Transition Via Repression of PI3K/Akt, ERK1/2 and Smad2/3 Pathway in Human Lung Carcinoma A549 Cells

REFERENCES

• Hay , E D . 1995 . An overview of epithelio-mesenchymal transformation . Acta Anat , 154 : 8 – 20 .
   PubMedGoogle Scholar
• Savagner , P . 2001 . Leaving the neighborhood: molecular mechanisms involved during epithelial–mesenchymal transition . Bioassays , 23 : 912 – 923 .
   PubMed Web of Science ®Google Scholar
• Thiery , J P . 2002 . Epithelial–mesenchymal transitions in tumour progression . Nat Rev Cancer , 2 : 442 – 454 .
   PubMed Web of Science ®Google Scholar
• Sun , D , Baur , S and Hay , E D . 2000 . Epithelial–mesenchymal transformation is the mechanism for fusion of the craniofacial primordial involved in morphogenesis of the chicken lip . Dev Biol , 228 : 337 – 349 .
   PubMed Web of Science ®Google Scholar
• Docherty , N G , O’Sullivan , O E , Healy , D A , Murphy , M O’neill , A J . 2006 . TGF-β1-induced EMT can occur independently of its proapoptotic effects and is aided by EGF receptor activation . Am J Physiol Renal Physiol , 290 : F1202 – F1212 .
   PubMed Web of Science ®Google Scholar
• Holian , J , Qi , W , Kelly , D J , Zhang , Y Mreich , E . 2008 . Role of Kruppel-like factor 6 in transforming growth factor-β1-induced epithelial-mesenchymal transition of proximal tubule cells . Am J Physiol Renal Physiol , 295 : F1388 – F1396 .
   PubMed Web of Science ®Google Scholar
• Heldin , C H , Miyazono , K and ten Dijke , P . 1997 . TGF-beta signalling from cell membrane to nucleus through SMAD proteins . Nature , 390 : 465 – 471 .
   PubMed Web of Science ®Google Scholar
• Derynck , R and Zhang , Y E . 2003 . Smad-dependent and Smad-independent pathways in TGFβ family signalling . Nature , 425 : 577 – 584 .
   PubMed Web of Science ®Google Scholar
• Nakao , A , Afrakhte , M , Moren , A , Nakayama , T Christian , J L . 1997 . Indentification of Smad7, a TGF beta-inducible antagonist of TGF beta signaling . Nature , 389 : 631 – 635 .
   PubMed Web of Science ®Google Scholar
• Siegel , P M and Massague , J . 2003 . Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer . Nat Rev Cancer , 3 : 807 – 821 .
   PubMed Web of Science ®Google Scholar
• Piek , E , Moustakas , A , Kurisaki , A , Heldin , C H and ten Dijke , P . 1999 . TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cell . J Cell Sci , 112 : 4557 – 4568 .
   PubMed Web of Science ®Google Scholar
• Bakin , A V , Tomlinson , A K , Bhowmick , N A , Moses , H L and Arteaga , C L . 2000 . Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration . J Biol Chem , 275 : 36803 – 36810 .
   PubMed Web of Science ®Google Scholar
• Bhowmick , N A , Ghiassi , M , Bakin , A , Aakre , M Lundquist , C A . 2001 . Transforming growth factorbeta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism . Mol Biol Cell , 12 : 27 – 36 .
   PubMed Web of Science ®Google Scholar
• Yu , L , Hebert , M C and Zhang , Y E . 2002 . TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses . EMBO J , 21 : 3749 – 3759 .
   PubMed Web of Science ®Google Scholar
• Massague , J , Blain , S and Lo , R . 2000 . TGFβ signaling in growth control, cancer and heritable disorders . Cell , 103 : 295 – 309 .
   PubMed Web of Science ®Google Scholar
• Souchelnytskyi , S . 2002 . Transforming growth factor-β signaling and its role in cancer . Exp Oncol , 24 : 3 – 12 .
   Web of Science ®Google Scholar
• Ciftci , K , Su , J and Trovitch , P B . 2003 . Growth factors and chemotherapeutic modulation of breast cancer cells . J Pharm Pharmacol , 55 : 1135 – 1141 .
   PubMed Web of Science ®Google Scholar
• Koutsilieris , M , Reyes-Moreno , C , Choki , I , Sourla , A Doillon , C . 1999 . Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by osteoblast-derived growth factors . Mol Med , 5 : 86 – 97 .
   PubMed Web of Science ®Google Scholar
• Tsuchida , K , Sunada , Y , Noji , S , Murakami , T Uezumi , A . 2006 . Inhibitors of the TGF-beta superfamily and their clinical applications . Mini Rev Med Chem , 6 : 1255 – 1261 .
   PubMed Web of Science ®Google Scholar
• Saunier , E F and Akhurst , R J . 2006 . TGF beta inhibition for cancer therapy . Curr Cancer Drug Targets , 6 : 565 – 578 .
   PubMed Web of Science ®Google Scholar
• Lee , E B . 1973 . Pharmacological studies on Platycodon grandiflorum A DC. IV. A comparison of experimental pharmacological effects of crude platycodin with clinical indications of platycodi radix . Yakugaku Zasshi , 93 : 1188 – 1194 .
   PubMed Web of Science ®Google Scholar
• Kim , K S , Ezaki , O , Ikemoto , S and Itakura , H . 1995 . Effects of Platycodon grandiflorum feeding on serum and liver lipid concentrations in rats with diet-induced hyperlipidemia . J Nutr Sci Vitaminol , 41 : 485 – 491 .
   PubMed Web of Science ®Google Scholar
• Lee , K J , Hwang , S J , Choi , J H and Jeong , H G . 2008 . Saponins derived from the roots of Platycodon grandiflorum inhibit HT-1080 cell invasion and MMPs activities: regulation of NF-kappaB activation via ROS signal pathway . Cancer Lett , 268 : 233 – 243 .
   PubMed Web of Science ®Google Scholar
• Lee , K J , Choi , J H , Kim , H G , Han , E H Hwang , Y P . 2008 . Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice . Food Chem Toxicol , 46 : 1778 – 1785 .
   PubMed Web of Science ®Google Scholar
• Khanal , T , Choi , J H , Hwang , Y P , Chung , Y C and Jeong , H G . 2009 . Saponins isolated from the root of Platycodon grandiflorum protect against acute ethanol-induced hepatotoxicity in mice . Food Chem Toxicol , 47 : 530 – 535 .
   PubMed Web of Science ®Google Scholar
• Khanal , T , Choi , J H , Hwang , Y P , Chung , Y C and Jeong , H G . 2009 . Protective effects of saponins from the root of Platycodon grandiflorum against fatty liver in chronic ethanol feeding via the activation of AMP-dependent protein kinase . Food Chem Toxicol , 47 : 2749 – 2754 .
   PubMed Web of Science ®Google Scholar
• Choi , J H , Hwang , Y P , Han , E H , Kim , H G Park , B H . 2011 . Inhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorum root-derived saponin in A549 cells . Food Chem Toxicol , 49 : 2157 – 2166 .
   PubMed Web of Science ®Google Scholar
• Lee , K J and Jeong , H G . 2002 . Protective effect of Platycodi radix on carbon tetrachloride-induced hepatotoxicity . Food Chem Toxicol , 40 : 517 – 525 .
   PubMed Web of Science ®Google Scholar
• Lee , K J , You , H J , Park , S J , Kim , Y S Chung , Y C . 2001 . Hepatoprotective effects of Platycodon grandiflorum on acetaminophen-induced liver damage in mice . Cancer Lett , 174 : 73 – 81 .
   PubMed Web of Science ®Google Scholar
• Lee , K J , Kim , J Y , Jung , K S , Choi , C Y Chung , Y C . 2004 . Suppressive effects of Platycodon grandiflorum on the progress of carbon tetrachloride-induced hepatic fibrosis . Arch Pharm Res , 27 : 1238 – 1244 .
   PubMed Web of Science ®Google Scholar
• Tada , A , Kaneiwa , Y , Shoji , J and Shibata , S . 1975 . Studies on the saponins of the root of Platycodon grandiflorum A. De Candolle I. Isolation and the structure of platycodin-D . Chem Pharm Bull , 23 : 2965 – 2972 .
   PubMed Web of Science ®Google Scholar
• Moustakas , A , Pardali , K , Gaal , A and Heldin , C H . 2002 . Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation . Immunol Lett , 82 : 85 – 91 .
   PubMed Web of Science ®Google Scholar
• Zhou , B P , Deng , J , Xia , W , Xu , J Li , Y M . 2004 . Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial–mesenchymal transition . Nat Cell Biol , 6 : 931 – 940 .
   PubMed Web of Science ®Google Scholar
• Kim , L and Kimmel , A R . 2000 . GSK3, a master switch regulating cell-fate specification and tumorigenesis . Curr Opin Genet Dev , 10 : 508 – 514 .
   PubMed Web of Science ®Google Scholar
• Bachelder , R E , Yoon , S O , Franci , C , de Herreros , A G and Mercurio , A M . 2005 . Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition . J Cell Biol , 168 : 29 – 33 .
   PubMed Web of Science ®Google Scholar
• Shin , J A , Hong , O K , Lee , H J , Jeon , S Y Kim , J W . 2011 . Transforming growth factor-β induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells . J Cell Biochem , 112 : 179 – 188 .
   PubMed Web of Science ®Google Scholar
• Sadej , R , Romanska , H , Kavanagh , D , Baldwin , G Takahashi , T . 2010 . Tetraspanin CD151 regulates transforming growth factor beta signaling: implication in tumor metastasis . Cancer Res , 70 : 6059 – 6070 .
   PubMed Web of Science ®Google Scholar
• Hayashi , H , Abdollah , S , Qiu , Y , Cai , J Xu , Y Y . 1997 . The MAD-related protein Smad7 associates with the TGF beta receptor and functions as an antagonist of TGF beta signaling . Cell , 89 : 1165 – 1173 .
   PubMed Web of Science ®Google Scholar
• Gupta , G P and Massagué , J . 2006 . Cancer metastasis: building a framework . Cell , 127 : 679 – 695 .
   PubMed Web of Science ®Google Scholar
• Lamouille , S and Derynck , R . 2011 . Emergence of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin axis in transforming growth factor-β-induced epithelial-mesenchymal transition . Cells Tissues Organs , 193 : 8 – 22 .
   PubMed Web of Science ®Google Scholar
• Willis , B C and Borok , Z . 2007 . TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease . Am J Physiol Lung Cell Mol Physiol , 293 : L525 – L534 .
   PubMed Web of Science ®Google Scholar
• Julien , S , Puig , I , Caretti , E , Bonaventure , J Nelles , L . 2007 . Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition . Oncogene , 26 : 7445 – 7456 .
   PubMed Web of Science ®Google Scholar
• Davies , M , Robinson , M , Smith , E , Huntley , S Prime , S . 2005 . Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling pathways . J Cell Biochem , 95 : 918 – 931 .
   PubMed Web of Science ®Google Scholar
• Caraci , F , Gili , E , Calafiore , M , Failla , M La Rosa , C . 2008 . TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts . Pharmacol Res , 57 : 274 – 282 .
   PubMed Web of Science ®Google Scholar
• Conte , E , Fruciano , M , Fagone , E , Gili , E Caraci , F . 2011 . Inhibition of PI3K Prevents the Proliferation and Differentiation of Human Lung Fibroblasts into Myofibroblasts: The Role of Class I P110 Isoforms . PLoS One , 6 : 1 – 10 .
   Web of Science ®Google Scholar
• Kattla , J J , Carew , R M , Heljic , M , Godson , C and Brazil , D P . 2008 . Protein kinase B/Akt activity is involved in renal TGF-β1-driven epithelial–mesenchymal transition in vitro and in vivo . Am J Physiol Renal Physiol , 295 : F215 – F225 .
   PubMed Web of Science ®Google Scholar
• Xu , J , Lamouille , S and Derynck , R . 2009 . TGF-beta-induced epithelial to mesenchymal transition . Cell Res , 19 : 156 – 172 .
   PubMed Web of Science ®Google Scholar
• Kaimori , A , Potter , J , Kaimori , J Y , Wang , C Mezey , E . 2007 . Transforming growth factor-beta1 induces an epithelial-to-mesenchymal transition state in mouse hepatocytes in vitro . J Biol Chem , 282 : 22089 – 22101 .
   PubMed Web of Science ®Google Scholar
• Kasai , H , Allen , J T , Mason , R M , Kamimura , T and Zhang , Z . 2005 . TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT) . Respir Res , 6 : 1 – 15 .
   PubMed Web of Science ®Google Scholar
• Noh , J R , Kim , Y H , Gang , G T , Yang , K J , Kim , S K , Ryu , S Y , Kim , Y S , Lee , C H and Lee , H S . 2010 . Preventative effects of Platycodon grandiflorum treatment on hepatic steatosis in high fat diet-fed C57BL/6 mice . Biological and pharmaceutical bulletin , 33 : 450 – 454 .
   PubMed Web of Science ®Google Scholar
• Ryu , C S , Kim , C H , Lee , S Y , Lee , K S , Choung , K J , Song , G Y , Kim , B H , Ryu , S Y , Lee , H S and Kim , S K . 2012 . Evaluation of the total oxidant scavenging capacity of saponins isolated from Platycodon grandiflorum . Food Chemistry , 132 : 333 – 337 .
   Web of Science ®Google Scholar
• Barcellos-Hoff , M H and Akhurst , R J . 2009 . Transforming growth factor-beta in breast cancer: too much, too late . Breast cancer research , 11 : 1 – 6 .
   Web of Science ®Google Scholar
• Park , C Y , Son , J Y , Jin , C H , Nam , J S , Kim , D K and Sheen , Y Y . 2011 . EW-7195, a novel inhibitor of ALK5 kinase inhibits EMT and breast cancer metastasis to lung . European journal of cancer , 47 : 2642 – 2653 .
   PubMed Web of Science ®Google Scholar
• Pennison , M and Pasche , B . 2007 . Targeting transforming growth factor-beta signaling . Current opinion in oncology , 19 : 579 – 585 .
   PubMed Web of Science ®Google Scholar
• Halder , S K , Beauchamp , R D and Datta , P K . 2005 . A specific inhibitor of TGF-beta receptor kinase, SB-431542, as a potent antitumor agent for human cancers . Neoplasia , 7 : 509 – 521 .
   PubMed Web of Science ®Google Scholar
• Ge , R , Rajeev , V , Ray , P , Lattime , E , Rittling , S , Medicherla , S , Protter , A , Murphy , A , Chakravarty , J , Dugar , S , Schreiner , G , Barnard , N and Reiss , M . 2006 . Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo . Clinical cancer research , 12 : 4315 – 4330 .
   PubMed Web of Science ®Google Scholar
• Rausch , M P , Hahn , T , Ramanathapuram , L , Bradley-Dunlop , D , Mahadevan , D , Mercado-Pimentel , M E , Runyan , R B , Besselsen , D G , Zhang , X , Cheung , H K , Lee , W C , Ling , L E and Akporiaye , E T . 2009 . An orally active small molecule TGF-beta receptor I antagonist inhibits the growth of metastatic murine breast cancer . Anticancer research , 29 : 2099 – 2109 .
   PubMed Web of Science ®Google Scholar
• Nam , J S , Terabe , M , Mamura , M , Kang , M J , Chae , H , Stuelten , C , Kohn , E , Tang , B , Sabzevari , H , Anver , M R , Lawrence , S , Danielpour , D , Lonning , S , Berzofsky , J A and Wakefield , L M . 2008 . An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments . Cancer research , 68 : 3835 – 3843 .
   PubMed Web of Science ®Google Scholar
• Zhao , B M and Hoffmann , F M . 2006 . Inhibition of transforming growth factor-beta1-induced signaling and epithelial-to-mesenchymal transition by the Smad-binding peptide aptamer Trx-SARA . Molecular biology of the cell , 17 : 3819 – 3831 .
   PubMed Web of Science ®Google Scholar