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Erschienen in: Tumor Biology 7/2016

06.01.2016 | Original Article

The attenuation of epithelial to mesenchymal transition and induction of anoikis by gigantol in human lung cancer H460 cells

verfasst von: Thitita Unahabhokha, Pithi Chanvorachote, Varisa Pongrakhananon

Erschienen in: Tumor Biology | Ausgabe 7/2016

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Abstract

Lung cancer has been the major cause of death within patients due to the high metastatic rate. One of the most essential processes of metastasis is the ability of cancer cells to resist the programmed cell death in a detached condition called anoikis. The discoveries of new natural compound that is able to sensitize anoikis in cancer cells have garnered the most interest in cancer pharmaceutical science. Gigantol, a bibenzyl compound extracted from Dendrobium draconis, has been a promising natural derived compound for cancer therapy due to several cytotoxic effects in cancer cells. This study has demonstrated for the first time that gigantol significantly decreases lung cancer cells’ viability in a detached condition through anoikis and anchorage-independent assays. Western blotting analysis reveals that gigantol greatly decreases epithelial to mesenchymal transition (EMT) markers including N-cadherin, vimentin, and Slug leading to a significant suppression of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and caveolin-1 (cav-1) survival pathways during the detached condition. Therefore, gigantol could be a potential cancer therapeutic compound suggesting for further development for cancer therapy.
Literatur
1.
Zurück zum Zitat Chiarugi P, Giannoni E. Anoikis: a necessary death program for anchorage-dependent cells. Biochem Pharmacol. 2008;76(11):1352–64.PubMedCrossRef Chiarugi P, Giannoni E. Anoikis: a necessary death program for anchorage-dependent cells. Biochem Pharmacol. 2008;76(11):1352–64.PubMedCrossRef
2.
Zurück zum Zitat Paoli P, Giannoni E, Chiarugi P. Anoikis molecular pathways and its role in cancer progression. BBA Mol Cell Res. 2013;1833(12):3481–98. Paoli P, Giannoni E, Chiarugi P. Anoikis molecular pathways and its role in cancer progression. BBA Mol Cell Res. 2013;1833(12):3481–98.
3.
Zurück zum Zitat Guadamillas MC, Cerezo A, del Pozo MA. Overcoming anoikis—pathways to anchorage-independent growth in cancer. J Cell Sci. 2011;124(19):3189–97.PubMedCrossRef Guadamillas MC, Cerezo A, del Pozo MA. Overcoming anoikis—pathways to anchorage-independent growth in cancer. J Cell Sci. 2011;124(19):3189–97.PubMedCrossRef
4.
5.
Zurück zum Zitat Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ. 2008;16(1):3–11.PubMedPubMedCentralCrossRef Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ. 2008;16(1):3–11.PubMedPubMedCentralCrossRef
6.
Zurück zum Zitat Yilmaz M, Christofori G. EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009;28(1–2):15–33.PubMedCrossRef Yilmaz M, Christofori G. EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009;28(1–2):15–33.PubMedCrossRef
7.
Zurück zum Zitat Sabbah M, Emami S, Redeuilh G, Julien S, Prévost G, Zimber A, et al. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat. 2008;11(4–5):123–51.PubMedCrossRef Sabbah M, Emami S, Redeuilh G, Julien S, Prévost G, Zimber A, et al. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat. 2008;11(4–5):123–51.PubMedCrossRef
8.
Zurück zum Zitat Shi Y, Wu H, Zhang M, Ding L, Meng F, Fan X. Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol. 2013;8(1):1–1. Shi Y, Wu H, Zhang M, Ding L, Meng F, Fan X. Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol. 2013;8(1):1–1.
9.
Zurück zum Zitat Geiger TR, Peeper DS. Metastasis mechanisms. BBA Rev Cancer. 2009;1796(2):293–308. Geiger TR, Peeper DS. Metastasis mechanisms. BBA Rev Cancer. 2009;1796(2):293–308.
10.
Zurück zum Zitat Voulgari A, Pintzas A. Epithelial–mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. BBA Rev Cancer. 2009;1796(2):75–90. Voulgari A, Pintzas A. Epithelial–mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. BBA Rev Cancer. 2009;1796(2):75–90.
12.
Zurück zum Zitat Floor SL, Dumont JE, Maenhaut C, Raspe E. Hallmarks of cancer: of all cancer cells, all the time? Trends Mol Med. 2012;18(9):509–15.PubMedCrossRef Floor SL, Dumont JE, Maenhaut C, Raspe E. Hallmarks of cancer: of all cancer cells, all the time? Trends Mol Med. 2012;18(9):509–15.PubMedCrossRef
13.
Zurück zum Zitat Powan P, Chanvorachote P. Nitric oxide mediates cell aggregation and mesenchymal to epithelial transition in anoikis-resistant lung cancer cells. Mol Cell Biochem. 2014;393(1–2):237–45.PubMedCrossRef Powan P, Chanvorachote P. Nitric oxide mediates cell aggregation and mesenchymal to epithelial transition in anoikis-resistant lung cancer cells. Mol Cell Biochem. 2014;393(1–2):237–45.PubMedCrossRef
14.
Zurück zum Zitat Chanvorachote P, Pongrakhananon V, Halim H. Caveolin-1 regulates metastatic behaviors of anoikis resistant lung cancer cells. Mol Cell Biochem. 2014;399(1–2):291–302.PubMed Chanvorachote P, Pongrakhananon V, Halim H. Caveolin-1 regulates metastatic behaviors of anoikis resistant lung cancer cells. Mol Cell Biochem. 2014;399(1–2):291–302.PubMed
15.
Zurück zum Zitat Halim H, Luanpitpong S, Chanvorachote P. Acquisition of anoikis resistance up-regulates caveolin-1 expression in human non-small cell lung cancer cells. Anticancer Res. 2012;32(5):1649–58.PubMed Halim H, Luanpitpong S, Chanvorachote P. Acquisition of anoikis resistance up-regulates caveolin-1 expression in human non-small cell lung cancer cells. Anticancer Res. 2012;32(5):1649–58.PubMed
16.
Zurück zum Zitat Ravid D, Maor S, Werner H, Liscovitch M. Caveolin-1 inhibits anoikis and promotes survival signaling in cancer cells. Adv Enzyme Regul. 2006;46(1):163–75.PubMedCrossRef Ravid D, Maor S, Werner H, Liscovitch M. Caveolin-1 inhibits anoikis and promotes survival signaling in cancer cells. Adv Enzyme Regul. 2006;46(1):163–75.PubMedCrossRef
17.
Zurück zum Zitat Ho C-C, Huang P-H, Huang H-Y, Chen Y-H, Yang P-C, Hsu S-M. Up-regulated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation. Am J Pathol. 2010;161(5):1647–56.CrossRef Ho C-C, Huang P-H, Huang H-Y, Chen Y-H, Yang P-C, Hsu S-M. Up-regulated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation. Am J Pathol. 2010;161(5):1647–56.CrossRef
18.
Zurück zum Zitat Chunhacha P, Chanvorachote P. Roles of caveolin-1 on anoikis resistance in non small cell lung cancer. Int J Physiol. 2011;4(3):149–55. Chunhacha P, Chanvorachote P. Roles of caveolin-1 on anoikis resistance in non small cell lung cancer. Int J Physiol. 2011;4(3):149–55.
19.
Zurück zum Zitat Chanvorachote P. Epithelial-mesenchymal transition mediates anoikis resistance and enhances invasion in pleural effusion-derived human lung cancer cells. Oncol Lett. 2013;5:1043–47.PubMedPubMedCentral Chanvorachote P. Epithelial-mesenchymal transition mediates anoikis resistance and enhances invasion in pleural effusion-derived human lung cancer cells. Oncol Lett. 2013;5:1043–47.PubMedPubMedCentral
20.
Zurück zum Zitat Klongkumnuankarn P, Busaranon K, Chanvorachote P, Sritularak B, Jongbunprasert V, Likhitwitayawuid K. Cytotoxic and antimigratory activities of phenolic compounds from dendrobium brymerianum. J Evid Based Complementary Altern Med. 2015;1–9. Klongkumnuankarn P, Busaranon K, Chanvorachote P, Sritularak B, Jongbunprasert V, Likhitwitayawuid K. Cytotoxic and antimigratory activities of phenolic compounds from dendrobium brymerianum. J Evid Based Complementary Altern Med. 2015;1–9.
21.
Zurück zum Zitat Charoenrungruang S, Chanvorachote P, Sritularak B. Gigantol-induced apoptosis in lung cancer cell through mitochondrial-dependent pathway. TJPS. 2014;38:67–73. Charoenrungruang S, Chanvorachote P, Sritularak B. Gigantol-induced apoptosis in lung cancer cell through mitochondrial-dependent pathway. TJPS. 2014;38:67–73.
22.
Zurück zum Zitat Charoenrungruang S, Chanvorachote P, Sritularak B, Pongrakhananon V. Gigantol, a bibenzyl from Dendrobium draconis, inhibits the migratory behavior of non-small cell lung cancer cells. J Nat Prod. 2014;77(6):1359–66.PubMedCrossRef Charoenrungruang S, Chanvorachote P, Sritularak B, Pongrakhananon V. Gigantol, a bibenzyl from Dendrobium draconis, inhibits the migratory behavior of non-small cell lung cancer cells. J Nat Prod. 2014;77(6):1359–66.PubMedCrossRef
23.
Zurück zum Zitat Sritularak B, Anuwat M, Likhitwitayawuid K. A new phenanthrenequinone from Dendrobium draconis. J Asian Nat Prod Res. 2011;13(3):251–5.PubMedCrossRef Sritularak B, Anuwat M, Likhitwitayawuid K. A new phenanthrenequinone from Dendrobium draconis. J Asian Nat Prod Res. 2011;13(3):251–5.PubMedCrossRef
24.
Zurück zum Zitat Bailey KM, Liu J. Caveolin-1 up-regulation during epithelial to mesenchymal transition is mediated by focal adhesion kinase. J Biol Chem. 2008;283(20):13714–24.PubMedPubMedCentralCrossRef Bailey KM, Liu J. Caveolin-1 up-regulation during epithelial to mesenchymal transition is mediated by focal adhesion kinase. J Biol Chem. 2008;283(20):13714–24.PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Ha G-H, Park J-S, Breuer E-KY. TACC3 promotes epithelial-mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways. Cancer Lett. 2013;332(1):63–73.PubMedCrossRef Ha G-H, Park J-S, Breuer E-KY. TACC3 promotes epithelial-mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways. Cancer Lett. 2013;332(1):63–73.PubMedCrossRef
26.
Zurück zum Zitat Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 2006;6(6):449–58.PubMedCrossRef Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 2006;6(6):449–58.PubMedCrossRef
27.
Zurück zum Zitat Weigelt B, Peterse JL, van’t Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005;5(8):591–602.PubMedCrossRef Weigelt B, Peterse JL, van’t Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005;5(8):591–602.PubMedCrossRef
28.
Zurück zum Zitat Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol. 2008;19(3):294–308.PubMedCrossRef Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol. 2008;19(3):294–308.PubMedCrossRef
29.
Zurück zum Zitat Larue L, Bellacosa A. Epithelial–mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene. 2005;24(50):7443–54.PubMedCrossRef Larue L, Bellacosa A. Epithelial–mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene. 2005;24(50):7443–54.PubMedCrossRef
30.
Zurück zum Zitat Winitthana T, Lawanprasert S, Chanvorachote P. Triclosan potentiates epithelial-to-mesenchymal transition in anoikis-resistant human lung cancer cells. PLoS ONE. 2014;9(10), e110851.PubMedPubMedCentralCrossRef Winitthana T, Lawanprasert S, Chanvorachote P. Triclosan potentiates epithelial-to-mesenchymal transition in anoikis-resistant human lung cancer cells. PLoS ONE. 2014;9(10), e110851.PubMedPubMedCentralCrossRef
31.
Zurück zum Zitat Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42.PubMedCrossRef Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42.PubMedCrossRef
32.
Zurück zum Zitat Nurwidya F, Takahashi F, Murakami A, Takahashi K. Epithelial mesenchymal transition in drug resistance and metastasis of lung cancer. Cancer Res Treat. 2012;44(3):151–6.PubMedPubMedCentralCrossRef Nurwidya F, Takahashi F, Murakami A, Takahashi K. Epithelial mesenchymal transition in drug resistance and metastasis of lung cancer. Cancer Res Treat. 2012;44(3):151–6.PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Frisch SM, Schaller M, Cieply B. Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J Cell Sci. 2013;126(1):21–9.PubMedPubMedCentralCrossRef Frisch SM, Schaller M, Cieply B. Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J Cell Sci. 2013;126(1):21–9.PubMedPubMedCentralCrossRef
34.
35.
Zurück zum Zitat Enomoto A, Murakami H, Asai N, Morone N, Watanabe T, Kawai K, et al. Akt/PKB regulates actin organization and cell motility via girdin/APE. Dev Cell. 2005;9(3):389–402.PubMedCrossRef Enomoto A, Murakami H, Asai N, Morone N, Watanabe T, Kawai K, et al. Akt/PKB regulates actin organization and cell motility via girdin/APE. Dev Cell. 2005;9(3):389–402.PubMedCrossRef
36.
Zurück zum Zitat Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;9(1):59–71.PubMedCrossRef Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;9(1):59–71.PubMedCrossRef
37.
Zurück zum Zitat Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 2006;58(11):621–31.PubMedCrossRef Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 2006;58(11):621–31.PubMedCrossRef
38.
Zurück zum Zitat McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EWT, Chang F, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. BBA Mol Cell Res. 2007;1773(8):1263–84. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EWT, Chang F, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. BBA Mol Cell Res. 2007;1773(8):1263–84.
39.
Zurück zum Zitat Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2012;9–18. Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2012;9–18.
40.
Zurück zum Zitat Luanpitpong S, Talbott SJ, Rojanasakul Y, Nimmanit U, Pongrakhananon V, Wang L, Chanvorachote P. Regulation of lung cancer cell migration and invasion by reactive oxygen species and caveolin-1. J Biol Chem. 2010;38832–40. Luanpitpong S, Talbott SJ, Rojanasakul Y, Nimmanit U, Pongrakhananon V, Wang L, Chanvorachote P. Regulation of lung cancer cell migration and invasion by reactive oxygen species and caveolin-1. J Biol Chem. 2010;38832–40.
41.
Zurück zum Zitat Scheel C, Weinberg RA. Cancer stem cells and epithelial–mesenchymal transition: concepts and molecular links. Semin Cancer Biol. 2012;22(5–6):396–403.PubMedCrossRef Scheel C, Weinberg RA. Cancer stem cells and epithelial–mesenchymal transition: concepts and molecular links. Semin Cancer Biol. 2012;22(5–6):396–403.PubMedCrossRef
42.
Zurück zum Zitat Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.PubMedPubMedCentralCrossRef Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.PubMedPubMedCentralCrossRef
44.
Zurück zum Zitat Lobo NA, Shimono Y, Qian D, Clarke MF. The Biology of Cancer Stem Cells. Annu Rev Cell Dev Biol. 2007;23(1):675–99.PubMedCrossRef Lobo NA, Shimono Y, Qian D, Clarke MF. The Biology of Cancer Stem Cells. Annu Rev Cell Dev Biol. 2007;23(1):675–99.PubMedCrossRef
45.
Zurück zum Zitat Yongsanguanchai N, Pongrakhananon V, Mutirangura A, Rojanasakul Y, Chanvorachote P. Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells. Am J Physiol. 2015;308(2):89–100.CrossRef Yongsanguanchai N, Pongrakhananon V, Mutirangura A, Rojanasakul Y, Chanvorachote P. Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells. Am J Physiol. 2015;308(2):89–100.CrossRef
46.
Zurück zum Zitat Chen K, Huang YH, Chen JL. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Nat Commun. 2013;34(6):732–40. Chen K, Huang YH, Chen JL. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Nat Commun. 2013;34(6):732–40.
47.
Zurück zum Zitat Han L, Shi S, Gong T, Zhang Z, Sun X. Cancer stem cells—therapeutic implications and perspectives in cancer therapy. Acta Pharm Sin B. 2013;3(2):65–75.CrossRef Han L, Shi S, Gong T, Zhang Z, Sun X. Cancer stem cells—therapeutic implications and perspectives in cancer therapy. Acta Pharm Sin B. 2013;3(2):65–75.CrossRef
48.
Zurück zum Zitat Jung H-Y, Yang J. Unraveling the TWIST between EMT and cancer stemness. Stem Cells. 2015;16(1):1–2.CrossRef Jung H-Y, Yang J. Unraveling the TWIST between EMT and cancer stemness. Stem Cells. 2015;16(1):1–2.CrossRef
49.
Zurück zum Zitat Schmidt JM, Panzilius E, Bartsch HS, Irmler M, Beckers J, Kari V, et al. Stem-cell-like properties and epithelial plasticity arise as stable traits after transient twist1 activation. Cell Rep. 2015;10(2):131–9.PubMedCrossRef Schmidt JM, Panzilius E, Bartsch HS, Irmler M, Beckers J, Kari V, et al. Stem-cell-like properties and epithelial plasticity arise as stable traits after transient twist1 activation. Cell Rep. 2015;10(2):131–9.PubMedCrossRef
50.
Zurück zum Zitat Rajendran G, Dutta D, Hong J, Paul A, Saha B, Mahato B, et al. Inhibition of protein kinase C signaling maintains rat embryonic stem cell pluripotency. J Biol Chem. 2013;288(34):24351–62.PubMedPubMedCentralCrossRef Rajendran G, Dutta D, Hong J, Paul A, Saha B, Mahato B, et al. Inhibition of protein kinase C signaling maintains rat embryonic stem cell pluripotency. J Biol Chem. 2013;288(34):24351–62.PubMedPubMedCentralCrossRef
51.
Zurück zum Zitat Bhummaphan N, Chanvorachote P. Gigantol suppresses cancer stem cell-like phenotypes in lung cancer cells. J Evid Based Complement Altern Med. 2015;2015(3):1–10.CrossRef Bhummaphan N, Chanvorachote P. Gigantol suppresses cancer stem cell-like phenotypes in lung cancer cells. J Evid Based Complement Altern Med. 2015;2015(3):1–10.CrossRef
Metadaten
Titel
The attenuation of epithelial to mesenchymal transition and induction of anoikis by gigantol in human lung cancer H460 cells
verfasst von
Thitita Unahabhokha
Pithi Chanvorachote
Varisa Pongrakhananon
Publikationsdatum
06.01.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 7/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4717-z

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