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Published in: Journal of Cancer Research and Clinical Oncology 5/2010

01-05-2010 | Original Paper

Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins

Authors: Anna Litwiniec, Alina Grzanka, Anna Helmin-Basa, Lidia Gackowska, Dariusz Grzanka

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2010

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Abstract

Purpose

Senescence and cell death are fail-safe mechanisms protecting against tumorigenesis. Both these forms of cellular response could be induced in cancer cells, thus suppressing tumor progression. Therefore, to fully understand chemotherapeutic effects, not only symptoms of cell death, but also of senescence should be evaluated. Since the involvement of cytoskeleton components in these processes has been reported, changes in the organization and level of some cytoskeletal proteins may be indicative of cell fate.

Methods

We analyzed selected markers of senescence and cell death, including possible alterations in vimentin and G-actin cytoskeleton in A549 cells after treatment with doxorubicin. Light (SA-β-galactosidase), fluorescent (vimentin and G-actin labeling) and electron microscopic examinations along with flow cytometry methods (TUNEL, Annexin V/PI staining, cell cycle analysis, intracellular level of vimentin) were employed to determine the outcome of the treatment.

Results

Uncoupling between senescent cell morphology and stable cell cycle arrest occurred. Some differences in the organization and level of cytoskeletal proteins, especially of vimentin, like fluctuations in its level, were observed. On the other hand, G-actin seemed to be more stable than vimentin.

Conclusions

G-actin stability may imply its potential usefulness for permanent senescence detection. Along with slight to moderate cytoskeletal alterations, the obtained results suggest transient senescence-like state induction, followed by morphology typical of mitotic catastrophe in part of the A549 cells.
Literature
go back to reference Arthur CR, Gupton JT, Kellogg GE, Yeudall WA, Cabot MC, Newsham IF, Gewirtz DA (2007) Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03–14, a novel microtubule poison. Biochem Pharmacol 74:981–991. doi:10.1016/j.bcp.2007.07.003 PubMed Arthur CR, Gupton JT, Kellogg GE, Yeudall WA, Cabot MC, Newsham IF, Gewirtz DA (2007) Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03–14, a novel microtubule poison. Biochem Pharmacol 74:981–991. doi:10.​1016/​j.​bcp.​2007.​07.​003 PubMed
go back to reference Beauséjour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J (2003) Reversal of human senescence: roles of the p53 and p16 pathways. EMBO J 22:4212–4222. doi:10.1093/emboj/cdg417 PubMed Beauséjour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J (2003) Reversal of human senescence: roles of the p53 and p16 pathways. EMBO J 22:4212–4222. doi:10.​1093/​emboj/​cdg417 PubMed
go back to reference Binaschi M, Capranico G, Dal Bo L, Zunino F (1997) Relationship between lethal effects and topoisomerase II mediated double-strand DNA breaks produced by anthracyclines with different sequence specificity. Mol Pharmacol 51:1053–1059PubMed Binaschi M, Capranico G, Dal Bo L, Zunino F (1997) Relationship between lethal effects and topoisomerase II mediated double-strand DNA breaks produced by anthracyclines with different sequence specificity. Mol Pharmacol 51:1053–1059PubMed
go back to reference Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dörken B, Jenuwein T, Schmitt CA (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436:660–665. doi:10.1038/nature03841 PubMed Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dörken B, Jenuwein T, Schmitt CA (2005) Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436:660–665. doi:10.​1038/​nature03841 PubMed
go back to reference Bursch W, Hochegger K, Török L, Marian B, Ellinger A, Hermann RS (2000) Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. J Cell Sci 113:1189–1198PubMed Bursch W, Hochegger K, Török L, Marian B, Ellinger A, Hermann RS (2000) Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. J Cell Sci 113:1189–1198PubMed
go back to reference Byun Y, Chen F, Chang R, Trivedi M, Green KJ, Cryns VL (2001) Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis. Cell Death Differ 8:443–450. doi:10.1038/sj.cdd.4400840 PubMed Byun Y, Chen F, Chang R, Trivedi M, Green KJ, Cryns VL (2001) Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis. Cell Death Differ 8:443–450. doi:10.​1038/​sj.​cdd.​4400840 PubMed
go back to reference Chang B-D, Swift ME, Shen M, Fang J, Broude EV, Roninson IB (2002) Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci USA 99:389–394. doi:10.1073/pnas.012602599 PubMed Chang B-D, Swift ME, Shen M, Fang J, Broude EV, Roninson IB (2002) Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci USA 99:389–394. doi:10.​1073/​pnas.​012602599 PubMed
go back to reference Chen Z, Trotman LC, Shaffer D, Lin H-K, Dotan ZA, Niki M, Koutcher JA, Scher HI, Ludwig T, Gerald W, Cordon-Cardo C, Pandolfi PP (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436:725–730. doi:10.1038/nature03918 PubMed Chen Z, Trotman LC, Shaffer D, Lin H-K, Dotan ZA, Niki M, Koutcher JA, Scher HI, Ludwig T, Gerald W, Cordon-Cardo C, Pandolfi PP (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436:725–730. doi:10.​1038/​nature03918 PubMed
go back to reference Croce MV, Colussi AG, Price MR, Segal-Eiras A (1999) Identification and characterization of different subpopulations in a human lung adenocarcinoma cell line (A549). Pathol Oncol Res 5:197–204. doi:10.1053/paor.1999.0212 PubMed Croce MV, Colussi AG, Price MR, Segal-Eiras A (1999) Identification and characterization of different subpopulations in a human lung adenocarcinoma cell line (A549). Pathol Oncol Res 5:197–204. doi:10.​1053/​paor.​1999.​0212 PubMed
go back to reference Di Felice V, Ardizzone N, Marcianò V, Bartolotta T, Cappello F, Farina F, Zummo G (2005) Senescence-associated HSP60 expression in normal human skin fibroblasts. Anat Rec Discov Mol Cell Evol Biol A 284:446–453 Di Felice V, Ardizzone N, Marcianò V, Bartolotta T, Cappello F, Farina F, Zummo G (2005) Senescence-associated HSP60 expression in normal human skin fibroblasts. Anat Rec Discov Mol Cell Evol Biol A 284:446–453
go back to reference Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363–9367. doi:10.1073/pnas.92.20.9363 PubMed Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363–9367. doi:10.​1073/​pnas.​92.​20.​9363 PubMed
go back to reference Dimri GP, Itahana K, Acosta M, Campisi J (2000) Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14ARF tumor suppressor. Mol Cell Biol 20:273–285PubMed Dimri GP, Itahana K, Acosta M, Campisi J (2000) Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14ARF tumor suppressor. Mol Cell Biol 20:273–285PubMed
go back to reference Dinsdale D, Lee JC, Dewson G, Cohen GM, Peter ME (2004) Intermediate filaments control the intracellular distribution of caspases during apoptosis. Am J Pathol 164:395–407PubMed Dinsdale D, Lee JC, Dewson G, Cohen GM, Peter ME (2004) Intermediate filaments control the intracellular distribution of caspases during apoptosis. Am J Pathol 164:395–407PubMed
go back to reference Douarre C, Gomez D, Morjani H, Zahm JM, O’donohue MF, Eddabra L, Mailliet P, Riou JF, Trentesaux C (2005) Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence. Nucleic Acids Res 33:2192–2203. doi:10.1093/nar/gki514 PubMed Douarre C, Gomez D, Morjani H, Zahm JM, O’donohue MF, Eddabra L, Mailliet P, Riou JF, Trentesaux C (2005) Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence. Nucleic Acids Res 33:2192–2203. doi:10.​1093/​nar/​gki514 PubMed
go back to reference Dulić V, Beney G-E, Frebourg G, Drullinger LF, Stein GH (2000) Uncoupling between phenotypic senescence and cell cycle arrest in aging p21-deficient fibroblasts. Mol Cell Biol 20:6741–6754PubMed Dulić V, Beney G-E, Frebourg G, Drullinger LF, Stein GH (2000) Uncoupling between phenotypic senescence and cell cycle arrest in aging p21-deficient fibroblasts. Mol Cell Biol 20:6741–6754PubMed
go back to reference Dunaief JL, Strober BE, Guha S, Khavari PA, Alin K, Luban J, Begemann M, Crabtree GR, Goff SP (1994) The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 79:119–130. doi:10.1016/0092-8674(94)90405-7 PubMed Dunaief JL, Strober BE, Guha S, Khavari PA, Alin K, Luban J, Begemann M, Crabtree GR, Goff SP (1994) The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 79:119–130. doi:10.​1016/​0092-8674(94)90405-7 PubMed
go back to reference Edelman MJ, Quam H, Mullins B (2001) Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines. Cancer Chemother Pharmacol 48:141–144. doi:10.1007/s002800000273 PubMed Edelman MJ, Quam H, Mullins B (2001) Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines. Cancer Chemother Pharmacol 48:141–144. doi:10.​1007/​s002800000273 PubMed
go back to reference Eom Y-W, Kim MA, Park SS, Goo MJ, Kwon HJ, Sohn S, Kim W-H, Yoon G, Choi KS (2005) Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene 24:4765–4777. doi:10.1038/sj.onc.1208627 PubMed Eom Y-W, Kim MA, Park SS, Goo MJ, Kwon HJ, Sohn S, Kim W-H, Yoon G, Choi KS (2005) Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene 24:4765–4777. doi:10.​1038/​sj.​onc.​1208627 PubMed
go back to reference Fang L, Igarashi M, Leung J, Sugrue MM, Lee SW, Aaronson SA (1999) p21Waf1/Cip1/Sdi1 induces permanent growth arrest with markers of replicative senescence in human tumor cells lacking functional p53. Oncogene 18:2789–2797. doi:10.1038/sj.onc.1202615 PubMed Fang L, Igarashi M, Leung J, Sugrue MM, Lee SW, Aaronson SA (1999) p21Waf1/Cip1/Sdi1 induces permanent growth arrest with markers of replicative senescence in human tumor cells lacking functional p53. Oncogene 18:2789–2797. doi:10.​1038/​sj.​onc.​1202615 PubMed
go back to reference Foster KA, Oster CG, Mayer MM, Avery ML, Audus KL (1998) Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism. Exp Cell Res 243:359–366. doi:10.1006/excr.1998.4172 PubMed Foster KA, Oster CG, Mayer MM, Avery ML, Audus KL (1998) Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism. Exp Cell Res 243:359–366. doi:10.​1006/​excr.​1998.​4172 PubMed
go back to reference Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, Parks WP (1973) In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 51:1417–1423PubMed Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, Parks WP (1973) In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 51:1417–1423PubMed
go back to reference Grzanka A, Grzanka D, Orlikowska M (2003) Cytoskeletal reorganization during process of apoptosis induced by cytostatic drugs in K-562 and HL-60 leukemia cell lines. Biochem Pharmacol 66:1611–1617. doi:10.1016/S0006-2952(03)00532-X PubMed Grzanka A, Grzanka D, Orlikowska M (2003) Cytoskeletal reorganization during process of apoptosis induced by cytostatic drugs in K-562 and HL-60 leukemia cell lines. Biochem Pharmacol 66:1611–1617. doi:10.​1016/​S0006-2952(03)00532-X PubMed
go back to reference Guénal I, Risler Y, Mignotte B (1997) Down-regulation of actin genes precedes microfilament network disruption and actin cleavage during p53-mediated apoptosis. J Cell Sci 110:489–495PubMed Guénal I, Risler Y, Mignotte B (1997) Down-regulation of actin genes precedes microfilament network disruption and actin cleavage during p53-mediated apoptosis. J Cell Sci 110:489–495PubMed
go back to reference Haynes A, Shaik MS, Chatterjee A, Singh M (2003) Evaluation of an aerosolized selective COX-2 inhibitor as a potentiator of doxorubicin in a non-small-cell lung cancer cell line. Pharm Res 20:1485–1495. doi:10.1023/A:1025774630993 PubMed Haynes A, Shaik MS, Chatterjee A, Singh M (2003) Evaluation of an aerosolized selective COX-2 inhibitor as a potentiator of doxorubicin in a non-small-cell lung cancer cell line. Pharm Res 20:1485–1495. doi:10.​1023/​A:​1025774630993 PubMed
go back to reference He Y, Fan S, Jiang Y (2005) p73 gene overexpression induces apoptosis and increases chemosensitivity in human lung adenocarcinoma cells A549. Int J Oncol 3:1 He Y, Fan S, Jiang Y (2005) p73 gene overexpression induces apoptosis and increases chemosensitivity in human lung adenocarcinoma cells A549. Int J Oncol 3:1
go back to reference Hoffman PC, Mauer AM, Vokes EE (2000) Lung cancer. Lancet 355:479–485PubMed Hoffman PC, Mauer AM, Vokes EE (2000) Lung cancer. Lancet 355:479–485PubMed
go back to reference Hukkanen J, Lassila A, Päivärinta K, Valanne S, Sarpo S, Hakkola J, Pelkonen O, Raunio H (2000) Induction and regulation of xenobiotic-metabolizing cytochrome P450 s in the human A549 lung adenocarcinoma cell line. Am J Respir Cell Mol Biol 22:360–366PubMed Hukkanen J, Lassila A, Päivärinta K, Valanne S, Sarpo S, Hakkola J, Pelkonen O, Raunio H (2000) Induction and regulation of xenobiotic-metabolizing cytochrome P450 s in the human A549 lung adenocarcinoma cell line. Am J Respir Cell Mol Biol 22:360–366PubMed
go back to reference Iavarone A, Massagué J (1997) Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-β in cells lacking the CDK inhibitor p15. Nature 387:417–422. doi:10.1038/387417a0 PubMed Iavarone A, Massagué J (1997) Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-β in cells lacking the CDK inhibitor p15. Nature 387:417–422. doi:10.​1038/​387417a0 PubMed
go back to reference Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G, Sherr CJ (1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19 ARF . Cell 91:649–659. doi:10.1016/S0092-8674(00)80452-3 PubMed Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G, Sherr CJ (1997) Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19 ARF . Cell 91:649–659. doi:10.​1016/​S0092-8674(00)80452-3 PubMed
go back to reference Katakura Y, Nakata E, Miura T, Shirahata S (1999) Transforming growth factor β triggers two independent-senescence programs in cancer cells. Biochem Biophys Res Commun 255:110–115. doi:10.1006/bbrc.1999.0129 PubMed Katakura Y, Nakata E, Miura T, Shirahata S (1999) Transforming growth factor β triggers two independent-senescence programs in cancer cells. Biochem Biophys Res Commun 255:110–115. doi:10.​1006/​bbrc.​1999.​0129 PubMed
go back to reference Klein LE, Freeze BS, Smith AB, Horwitz SB (2005) The microtubule stabilizing agent discodermolide is a potent inducer of accelerated senescence. Cell Cycle 4:501–507PubMed Klein LE, Freeze BS, Smith AB, Horwitz SB (2005) The microtubule stabilizing agent discodermolide is a potent inducer of accelerated senescence. Cell Cycle 4:501–507PubMed
go back to reference Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000) Senescence-associated β-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113:3613–3622PubMed Kurz DJ, Decary S, Hong Y, Erusalimsky JD (2000) Senescence-associated β-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci 113:3613–3622PubMed
go back to reference Lieber M, Smith B, Szakal A, Nelson-Rees W, Todaro G (1976) A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer 17:62–70. doi:10.1002/ijc.2910170110 PubMed Lieber M, Smith B, Szakal A, Nelson-Rees W, Todaro G (1976) A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer 17:62–70. doi:10.​1002/​ijc.​2910170110 PubMed
go back to reference Lim IK, Hong KW, Kwak IH, Yoon G, Park SC (2000) Cytoplasmic retention of p-Erk1/2 and nuclear accumulation of actin proteins during cellular senescence in human diploid fibroblasts. Mech Ageing Dev 119:113–129. doi:10.1016/S0047-6374(00)00167-6 PubMed Lim IK, Hong KW, Kwak IH, Yoon G, Park SC (2000) Cytoplasmic retention of p-Erk1/2 and nuclear accumulation of actin proteins during cellular senescence in human diploid fibroblasts. Mech Ageing Dev 119:113–129. doi:10.​1016/​S0047-6374(00)00167-6 PubMed
go back to reference Liu Y, El-Naggar S, Darling DS, Higashi Y, Dean DC (2008) Zeb1 links epithelial-mesenchymal transition and cellular senescence. Development 135:579–588. doi:10.1242/dev.007047 PubMed Liu Y, El-Naggar S, Darling DS, Higashi Y, Dean DC (2008) Zeb1 links epithelial-mesenchymal transition and cellular senescence. Development 135:579–588. doi:10.​1242/​dev.​007047 PubMed
go back to reference Lock RB, Stribinskiene L (1996) Dual modes of death induced by etoposide in human epithelial tumor cells allow Bcl-2 to inhibit apoptosis without affecting clonogenic survival. Cancer Res 56:4006–4012PubMed Lock RB, Stribinskiene L (1996) Dual modes of death induced by etoposide in human epithelial tumor cells allow Bcl-2 to inhibit apoptosis without affecting clonogenic survival. Cancer Res 56:4006–4012PubMed
go back to reference Meijerman I, Blom WM, de Bont HJGM, Mulder GJ, Nagelkerke JF (1997) Nuclear accumulation of G-actin in isolated rat hepatocytes by adenine nucleotides. Biochem Biophys Res Commun 240:697–700. doi:10.1006/bbrc.1997.7724 PubMed Meijerman I, Blom WM, de Bont HJGM, Mulder GJ, Nagelkerke JF (1997) Nuclear accumulation of G-actin in isolated rat hepatocytes by adenine nucleotides. Biochem Biophys Res Commun 240:697–700. doi:10.​1006/​bbrc.​1997.​7724 PubMed
go back to reference Meijerman I, Blom WM, de Bont HJGM, Mulder GJ, Nagelkerke JF (1999) Induction of apoptosis and changes in nuclear G-actin are mediated by different pathways: the effect of inhibitors of protein and RNA synthesis in isolated rat hepatocytes. Toxicol Appl Pharmacol 156:46–55. doi:10.1006/taap.1998.8616 PubMed Meijerman I, Blom WM, de Bont HJGM, Mulder GJ, Nagelkerke JF (1999) Induction of apoptosis and changes in nuclear G-actin are mediated by different pathways: the effect of inhibitors of protein and RNA synthesis in isolated rat hepatocytes. Toxicol Appl Pharmacol 156:46–55. doi:10.​1006/​taap.​1998.​8616 PubMed
go back to reference Meriwether WD, Bachur NR (1972) Inhibition of DNA and RNA metabolism by daunorubicin and adriamycin in L1210 mouse leukemia. Cancer Res 32:1137–1142PubMed Meriwether WD, Bachur NR (1972) Inhibition of DNA and RNA metabolism by daunorubicin and adriamycin in L1210 mouse leukemia. Cancer Res 32:1137–1142PubMed
go back to reference Mi J, Zhang X, Rabbani ZN, Liu Y, Reddy SK, Su Z, Salahuddin FK, Viles K, Giangrande PH, Dewhirst MW, Sullenger BA, Kontos CD, Clary BM (2008) RNA aptamer-targeted inhibition of NF-κB suppresses non-small cell lung cancer resistance to doxorubicin. Mol Ther 16:66–73. doi:10.1038/sj.mt.6300320 PubMed Mi J, Zhang X, Rabbani ZN, Liu Y, Reddy SK, Su Z, Salahuddin FK, Viles K, Giangrande PH, Dewhirst MW, Sullenger BA, Kontos CD, Clary BM (2008) RNA aptamer-targeted inhibition of NF-κB suppresses non-small cell lung cancer resistance to doxorubicin. Mol Ther 16:66–73. doi:10.​1038/​sj.​mt.​6300320 PubMed
go back to reference Michaloglou C, Vredeveld LCW, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436:720–724. doi:10.1038/nature03890 PubMed Michaloglou C, Vredeveld LCW, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS (2005) BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436:720–724. doi:10.​1038/​nature03890 PubMed
go back to reference Michishita E, Nakabayashi K, Ogino H, Suzuki T, Fujii M, Ayusawa D (1998) DNA topoisomerase inhibitors induce reversible senescence in normal human fibroblasts. Biochem Biophys Res Commun 253:667–671. doi:10.1006/bbrc.1998.9832 PubMed Michishita E, Nakabayashi K, Ogino H, Suzuki T, Fujii M, Ayusawa D (1998) DNA topoisomerase inhibitors induce reversible senescence in normal human fibroblasts. Biochem Biophys Res Commun 253:667–671. doi:10.​1006/​bbrc.​1998.​9832 PubMed
go back to reference Milzani A, Rossi R, Di Simplicio P, Giustarini D, Colombo R, DalleDonne I (2000) The oxidation produced by hydrogen peroxide on Ca-ATP-G-actin. Protein Sci 9:1774–1782. doi:10.1110/ps.9.9.1774 PubMed Milzani A, Rossi R, Di Simplicio P, Giustarini D, Colombo R, DalleDonne I (2000) The oxidation produced by hydrogen peroxide on Ca-ATP-G-actin. Protein Sci 9:1774–1782. doi:10.​1110/​ps.​9.​9.​1774 PubMed
go back to reference Mishima K, Handa JT, Aotaki-Keen A, Lutty GA, Morse LS, Hjelmeland LM (1999) Senescence-associated β-galactosidase histochemistry for the primate eye. Invest Ophthalmol Vis Sci 40:1590–1593PubMed Mishima K, Handa JT, Aotaki-Keen A, Lutty GA, Morse LS, Hjelmeland LM (1999) Senescence-associated β-galactosidase histochemistry for the primate eye. Invest Ophthalmol Vis Sci 40:1590–1593PubMed
go back to reference Moll UM, Ostermeyer AG, Haladay R, Winkfield B, Frazier M, Zambetti G (1996) Cytoplasmic sequestration of wild-type p53 protein impairs the G1 checkpoint after DNA damage. Mol Cell Biol 16:1126–1137PubMed Moll UM, Ostermeyer AG, Haladay R, Winkfield B, Frazier M, Zambetti G (1996) Cytoplasmic sequestration of wild-type p53 protein impairs the G1 checkpoint after DNA damage. Mol Cell Biol 16:1126–1137PubMed
go back to reference Mortenson MM, Schlieman MG, Virudachalam S, Bold RJ (2004) Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapy in the A549 non-small-cell lung cancer cell line. Cancer Chemother Pharmacol 54:343–353. doi:10.1007/s00280-004-0811-4 PubMed Mortenson MM, Schlieman MG, Virudachalam S, Bold RJ (2004) Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapy in the A549 non-small-cell lung cancer cell line. Cancer Chemother Pharmacol 54:343–353. doi:10.​1007/​s00280-004-0811-4 PubMed
go back to reference Moxham BL, Webb PP, Benjamin M, Ralphs JR (1998) Changes in the cytoskeleton of cells within the periodontal ligament and dental pulp of the rat first molar tooth during ageing. Eur J Oral Sci 106(Suppl 1):376–383PubMed Moxham BL, Webb PP, Benjamin M, Ralphs JR (1998) Changes in the cytoskeleton of cells within the periodontal ligament and dental pulp of the rat first molar tooth during ageing. Eur J Oral Sci 106(Suppl 1):376–383PubMed
go back to reference Nakanishi K, Maruyama M, Shibata T, Morishima N (2001) Identification of a caspase-9 substrate and detection of its cleavage in programmed cell death during mouse development. J Biol Chem 276:41237–41244. doi:10.1074/jbc.M105648200 PubMed Nakanishi K, Maruyama M, Shibata T, Morishima N (2001) Identification of a caspase-9 substrate and detection of its cleavage in programmed cell death during mouse development. J Biol Chem 276:41237–41244. doi:10.​1074/​jbc.​M105648200 PubMed
go back to reference Narita M, Nũnez S, Heard E, Narita M, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:703–716. doi:10.1016/S0092-8674(03)00401-X PubMed Narita M, Nũnez S, Heard E, Narita M, Lin AW, Hearn SA, Spector DL, Hannon GJ, Lowe SW (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113:703–716. doi:10.​1016/​S0092-8674(03)00401-X PubMed
go back to reference Nishio K, Inoue A (2005) Senescence-associated alterations of cytoskeleton: extraordinary production of vimentin that anchors cytoplasmic p53 in senescent human fibroblasts. Histochem Cell Biol 123:263–273. doi:10.1007/s00418-005-0766-5 PubMed Nishio K, Inoue A (2005) Senescence-associated alterations of cytoskeleton: extraordinary production of vimentin that anchors cytoplasmic p53 in senescent human fibroblasts. Histochem Cell Biol 123:263–273. doi:10.​1007/​s00418-005-0766-5 PubMed
go back to reference Nishio K, Inoue A, Qiao S, Kondo H, Mimura A (2001) Senescence and cytoskeleton: overproduction of vimentin induces senescent-like morphology in human fibroblasts. Histochem Cell Biol 116:321–327. doi:10.1007/s004180100325 PubMed Nishio K, Inoue A, Qiao S, Kondo H, Mimura A (2001) Senescence and cytoskeleton: overproduction of vimentin induces senescent-like morphology in human fibroblasts. Histochem Cell Biol 116:321–327. doi:10.​1007/​s004180100325 PubMed
go back to reference Okamoto A, Hussain SP, Hagiwara K, Spillare EA, Rusin MR, Demetrick DJ, Serrano M, Hannon GJ, Shiseki M, Zariwala M, Xiong Y, Beach DH, Yokota J, Harris CC (1995) Mutations in the p16 INK4/MTS1/CDKN2, p15 INK4B/MTS2, and p18 genes in primary and metastatic lung cancer. Cancer Res 55:1448–1451PubMed Okamoto A, Hussain SP, Hagiwara K, Spillare EA, Rusin MR, Demetrick DJ, Serrano M, Hannon GJ, Shiseki M, Zariwala M, Xiong Y, Beach DH, Yokota J, Harris CC (1995) Mutations in the p16 INK4/MTS1/CDKN2, p15 INK4B/MTS2, and p18 genes in primary and metastatic lung cancer. Cancer Res 55:1448–1451PubMed
go back to reference Otterson GA, Villalona-Calero MA, Sharma S, Kris MG, Imondi A, Gerber M, White DA, Ratain MJ, Schiller JH, Sandler A, Kraut M, Mani S, Murren JR (2007) Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. Clin Cancer Res 13:1246–1252. doi:10.1158/1078-0432.CCR-06-1096 PubMed Otterson GA, Villalona-Calero MA, Sharma S, Kris MG, Imondi A, Gerber M, White DA, Ratain MJ, Schiller JH, Sandler A, Kraut M, Mani S, Murren JR (2007) Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs. Clin Cancer Res 13:1246–1252. doi:10.​1158/​1078-0432.​CCR-06-1096 PubMed
go back to reference Patlakas G, Bouros D, Tsantekidou-Pozova S, Koukourakis MI (2005) Triplet chemotherapy with docetaxel, gemcitabine and liposomal doxorubicin, supported with subcutaneous amifostine and hemopoietic growth factors, in advanced non-small cell lung cancer. Anticancer Res 25:1427–1431PubMed Patlakas G, Bouros D, Tsantekidou-Pozova S, Koukourakis MI (2005) Triplet chemotherapy with docetaxel, gemcitabine and liposomal doxorubicin, supported with subcutaneous amifostine and hemopoietic growth factors, in advanced non-small cell lung cancer. Anticancer Res 25:1427–1431PubMed
go back to reference Pendleton A, Pope B, Weeds A, Koffer A (2003) Latrunculin B or ATP depletion induces cofilin-dependent translocation of actin into nuclei of mast cells. J Biol Chem 278:14394–14400. doi:10.1074/jbc.M206393200 PubMed Pendleton A, Pope B, Weeds A, Koffer A (2003) Latrunculin B or ATP depletion induces cofilin-dependent translocation of actin into nuclei of mast cells. J Biol Chem 278:14394–14400. doi:10.​1074/​jbc.​M206393200 PubMed
go back to reference Rando OJ, Zhao K, Janmey P, Crabtree GR (2002) Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex. Proc Natl Acad Sci USA 99:2824–2829. doi:10.1073/pnas.032662899 PubMed Rando OJ, Zhao K, Janmey P, Crabtree GR (2002) Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex. Proc Natl Acad Sci USA 99:2824–2829. doi:10.​1073/​pnas.​032662899 PubMed
go back to reference Riou JF, Guittat L, Mailliet P, Laoui A, Renou E, Petitgenet O, Mégnin-Chanet F, Hélène C, Mergny JL (2002) Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands. Proc Natl Acad Sci USA 99:2672–2677. doi:10.1073/pnas.052698099 PubMed Riou JF, Guittat L, Mailliet P, Laoui A, Renou E, Petitgenet O, Mégnin-Chanet F, Hélène C, Mergny JL (2002) Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands. Proc Natl Acad Sci USA 99:2672–2677. doi:10.​1073/​pnas.​052698099 PubMed
go back to reference Roberson RS, Kussick SJ, Vallieres E, Chen SY, Wu DY (2005) Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res 65:2795–2803. doi:10.1158/0008-5472.CAN-04-1270 PubMed Roberson RS, Kussick SJ, Vallieres E, Chen SY, Wu DY (2005) Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res 65:2795–2803. doi:10.​1158/​0008-5472.​CAN-04-1270 PubMed
go back to reference Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, Lowe SW (2002) A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109:335–346. doi:10.1016/S0092-8674(02)00734-1 PubMed Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, Lowe SW (2002) A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109:335–346. doi:10.​1016/​S0092-8674(02)00734-1 PubMed
go back to reference Seluanov A, Gorbunova V, Falcovitz A, Sigal A, Milyavsky M, Zurer I, Shohat G, Goldfinger N, Rotter V (2001) Change of the death pathway in senescent human fibroblasts in response to DNA damage is caused by an inability to stabilize p53. Mol Cell Biol 21:1552–1564. doi:10.1128/MCB.21.5.1552-1564.2001 PubMed Seluanov A, Gorbunova V, Falcovitz A, Sigal A, Milyavsky M, Zurer I, Shohat G, Goldfinger N, Rotter V (2001) Change of the death pathway in senescent human fibroblasts in response to DNA damage is caused by an inability to stabilize p53. Mol Cell Biol 21:1552–1564. doi:10.​1128/​MCB.​21.​5.​1552-1564.​2001 PubMed
go back to reference Sommers CL, Heckford SE, Skerker JM, Worland P, Torri JA, Thompson EW, Byers SW, Gelmann EP (1992) Loss of epithelial markers and acquisition of vimentin expression in adriamycin- and vinblastine-resistant human breast cancer cell lines. Cancer Res 52:5190–5197PubMed Sommers CL, Heckford SE, Skerker JM, Worland P, Torri JA, Thompson EW, Byers SW, Gelmann EP (1992) Loss of epithelial markers and acquisition of vimentin expression in adriamycin- and vinblastine-resistant human breast cancer cell lines. Cancer Res 52:5190–5197PubMed
go back to reference Stein GH, Drullinger LF, Soulard A, Dulić V (1999) Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol 19:2109–2117PubMed Stein GH, Drullinger LF, Soulard A, Dulić V (1999) Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol 19:2109–2117PubMed
go back to reference Sung J-M, Cho H-J, Yi H, Lee CH, Kim HS, Kim DK, Abd El-Aty AM, Kim JS, Landowski CP, Hediger MA, Shin HC (2008) Characterization of a stem cell population in lung cancer A549 cells. Biochem Biophys Res Commun 371:163–167. doi:10.1016/j.bbrc.2008.04.038 PubMed Sung J-M, Cho H-J, Yi H, Lee CH, Kim HS, Kim DK, Abd El-Aty AM, Kim JS, Landowski CP, Hediger MA, Shin HC (2008) Characterization of a stem cell population in lung cancer A549 cells. Biochem Biophys Res Commun 371:163–167. doi:10.​1016/​j.​bbrc.​2008.​04.​038 PubMed
go back to reference te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP (2002) DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 62:1876–1883PubMed te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP (2002) DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 62:1876–1883PubMed
go back to reference Thomson S, Buck E, Petti F, Griffin G, Brown E, Ramnarine N, Iwata KK, Gibson N, Haley JD (2005) Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 65:9455–9462. doi:10.1158/0008-5472.CAN-05-1058 PubMed Thomson S, Buck E, Petti F, Griffin G, Brown E, Ramnarine N, Iwata KK, Gibson N, Haley JD (2005) Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 65:9455–9462. doi:10.​1158/​0008-5472.​CAN-05-1058 PubMed
go back to reference Tolstonog GV, Shoeman RL, Traub U, Traub P (2001) Role of the intermediate filament protein vimentin in delaying senescence and in the spontaneous immortalization of mouse embryo fibroblasts. DNA Cell Biol 20:509–529. doi:10.1089/104454901317094945 PubMed Tolstonog GV, Shoeman RL, Traub U, Traub P (2001) Role of the intermediate filament protein vimentin in delaying senescence and in the spontaneous immortalization of mouse embryo fibroblasts. DNA Cell Biol 20:509–529. doi:10.​1089/​1044549013170949​45 PubMed
go back to reference Untergasser G, Koch HB, Menssen A, Hermeking H (2002) Characterization of epithelial senescence by serial analysis of gene expression: identification of genes potentially involved in prostate cancer. Cancer Res 62:6255–6262PubMed Untergasser G, Koch HB, Menssen A, Hermeking H (2002) Characterization of epithelial senescence by serial analysis of gene expression: identification of genes potentially involved in prostate cancer. Cancer Res 62:6255–6262PubMed
go back to reference Van der Loo B, Fenton MJ, Erusalimsky JD (1998) Cytochemical detection of a senescence-associated β-galactosidase in endothelial and smooth muscle cells from human and rabbit blood vessels. Exp Cell Res 241:309–315. doi:10.1006/excr.1998.4035 PubMed Van der Loo B, Fenton MJ, Erusalimsky JD (1998) Cytochemical detection of a senescence-associated β-galactosidase in endothelial and smooth muscle cells from human and rabbit blood vessels. Exp Cell Res 241:309–315. doi:10.​1006/​excr.​1998.​4035 PubMed
go back to reference Vartiainen MK, Guettler S, Larijani B, Treisman R (2007) Nuclear actin regulates dynamic, subcellular localization and activity of the SRF cofactor MAL. Science 316:1749–1752 Vartiainen MK, Guettler S, Larijani B, Treisman R (2007) Nuclear actin regulates dynamic, subcellular localization and activity of the SRF cofactor MAL. Science 316:1749–1752
go back to reference Wada A, Fukuda M, Mishima M, Nishida E (1998) Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein. EMBO J 17:1635–1641. doi:10.1093/emboj/17.6.1635 PubMed Wada A, Fukuda M, Mishima M, Nishida E (1998) Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein. EMBO J 17:1635–1641. doi:10.​1093/​emboj/​17.​6.​1635 PubMed
go back to reference Wang X, Wong SCH, Pan J, Tsao SW, Fung KHY, Kwong DLW, Sham JST, Nicholls JM (1998) Evidence of cisplatin-induced senescent-like growth arrest in nasopharyngeal carcinoma cells. Cancer Res 58:5019–5022PubMed Wang X, Wong SCH, Pan J, Tsao SW, Fung KHY, Kwong DLW, Sham JST, Nicholls JM (1998) Evidence of cisplatin-induced senescent-like growth arrest in nasopharyngeal carcinoma cells. Cancer Res 58:5019–5022PubMed
go back to reference Węsierska-Gądek J, Wojciechowski J, Ranftler C, Schmid G (2005) Role of p53 tumor suppressor in ageing: regulation of transient cell cycle arrest and terminal senescence. J Physiol Pharmacol 56:15–28PubMed Węsierska-Gądek J, Wojciechowski J, Ranftler C, Schmid G (2005) Role of p53 tumor suppressor in ageing: regulation of transient cell cycle arrest and terminal senescence. J Physiol Pharmacol 56:15–28PubMed
go back to reference Xie QC, Hu YD, Wang LL, Chen ZT, Diao XW, Wang ZX, Guan HJ, Zhu B, Sun JG, Duan YZ, Chen FL, Nian WQ (2005) The co-transfection of p16(INK4a) and p14(ARF) genes into human lung cancer cell line A549 and the effects on cell growth and chemosensitivity. Colloids Surf B Biointerfaces 46:188–196. doi:10.1016/j.colsurfb.2005.10.006 PubMed Xie QC, Hu YD, Wang LL, Chen ZT, Diao XW, Wang ZX, Guan HJ, Zhu B, Sun JG, Duan YZ, Chen FL, Nian WQ (2005) The co-transfection of p16(INK4a) and p14(ARF) genes into human lung cancer cell line A549 and the effects on cell growth and chemosensitivity. Colloids Surf B Biointerfaces 46:188–196. doi:10.​1016/​j.​colsurfb.​2005.​10.​006 PubMed
Metadata
Title
Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins
Authors
Anna Litwiniec
Alina Grzanka
Anna Helmin-Basa
Lidia Gackowska
Dariusz Grzanka
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 5/2010
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-009-0711-4

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