Depletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin
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Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli,which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy. [BMB reports 2011; 44(1): 46-51]
Abstract
Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli,which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy. [BMB reports 2011; 44(1): 46-51]
참고문헌 (39)
- Daw, N. C, "Metastatic osteosarcoma", Cancer, 106, pp.403~412 (2006)
- Bielack, S. S, "Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols", J. Clin. Oncol, 20, pp.776~790 (2002)
- Niswander, L. M, "Stratifying osteosarcoma: minimizing and maximizing therapy", Curr. Oncol. Rep, 12, pp.266~270 (2010)
- Orosco, A, "Syndecan-2 affects the basal and chemotherapy-induced apoptosis in osteosarcoma", Cancer Res, 67, pp.3708~3715 (2007)
- Sihn, C. R, "CANu1, a novel nucleolar protein, accumulated on centromere in response to DNA damage", GENES TO CELLS, 13(8), pp.787~796 (2008), BLACKWELL PUBLISHING
- Jung, M. Y, "Translational control by neuroguidin, a eukaryotic initiation factor 4E and CPEB binding protein", Mol. Cell Biol, 26, pp.4277~4287 (2006)
- Tembe, V, "Protein trafficking in response to DNA damage", Cell Signal, 19, pp.1113~1120 (2007)
- Mo, Y. Y, "Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the protein", J. Biol. Chem, 277, pp.2958~2964 (2002)
- Daniely, Y, "Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation", Mol. Cell Biol, 22, pp.6014~6222 (2002)
- Blander, G, "DNA damage-induced translocation of the Werner helicase is regulated by acetylation", J. Biol. Chem, 277, pp.50934~50940 (2002)
- Condemine, W, "A nucleolar targeting signal in PML-I addresses PML to nucleolar caps in stressed or senescent cells", J. Cell Sci, 120, pp.3219~3227 (2007)
- Kurki, S, "Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization", J. Cell Sci, 116, pp.3917~3925 (2003)
- Alastalo, T. P, "Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70", J. Cell Sci, 116, pp.3557~3570 (2003)
- Yuan, X. W, "Interferon-alpha enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis", Acta Pharmacol. Sin, 26, pp.1835~1841 (2007)
- Bruland, O. S, "On the current management of osteosarcoma. A critical evaluation and a proposal for a modified treatment strategy", Eur. J. Cancer, 33, pp.1725~1731 (1997)
- Lambert, L. A, "Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model", Cancer Res, 68, pp.7966~7974 (2008)
- Zucchi, R, "Cardiac toxicity of antineoplastic anthracyclines", Curr. Med. Chem. Anticancer Agents, 3, pp.151~171 (2003)
- Schimmel, K. J, "Cardiotoxicity of cytotoxic drugs", Cancer Treat. Rev, 30, pp.181~191 (2004)
- Liu, S, "Differential effects of cell cycle regulatory protein p21(WAF1", Cip1) on apoptosis and sensitivity to cancer chemotherapy, 2003, pp.6, 183~195
- Agrawal, S, "Stat1-dependent, p53-independent expression of p21(waf1) modulates oxysterolinduced apoptosis", Mol. Cell Biol, 22, pp.1981~1992 (2002)
- Teraishi, F, "Ectopic p21sdi1 gene transfer induces retinoic acid receptor beta expression and sensitizes human cancer cells to retinoid treatment", Int. J. Cancer, 103, pp.833~839 (2003)
- Lincet, H, "The p21 (cip1", waf1) cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells, 2000, pp.161, 17~26
- Qin, L. F, "Exogenous expression of p21(WAF1", CIP1) exerts cell growth inhibition and enhances sensitivity to cisplatin in hepatoma cells, 2001, pp.172, 7~15
- Klibanov, S. A, "Accumulation of soluble and nucleolar-associated p53 proteins following cellular stress", J. Cell Sci, 114, pp.1867~1873 (2001)
- Zhang, S, "Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2)", J. Cell Sci, 117, pp.3935~3945 (2004)
- Mayer, C, "Cellular stress and nucleolar function", Cell Cycle, 4, pp.1036~1038 (2005)
- Montanaro, L, "Nucleolus, ribosomes, and cancer", Am. J. Pathol, 173, pp.301~310 (2008)
- Derenzini, M, "What the nucleolus says to a tumour pathologist", Histopathology, 54, pp.753~762 (2008)
- Meng, L, "Nucleoplasmic mobilization of nucleostemin stabilizes MDM2 and promotes G2-M progression and cell survival", J. Cell Sci, 121, pp.4037~4046 (2008)
- Ma, H, "Nucleophosmin is a binding partner of nucleostemin in human osteosarcoma cells", Mol. Biol. Cell, 19, pp.2870~2875 (2008)
- Jafarnejad, S. M, "Knocking-down the expression of nucleostemin significantly decreases rate of proliferation of rat bone marrow stromal stem cells in an apparently p53-independent manner", Cell Prolif, 41, pp.28~35 (2008)
- Dai, M. S, "Aberrant expression of nucleostemin activates p53 and induces cell cycle arrest via inhibition of MDM2", Mol. Cell Biol, 28, pp.4365~4376 (2008)
- Woo, L. L, "The Rothmund-Thomson gene product RECQL4 localizes to the nucleolus in response to oxidative stress", Exp. Cell Res, 312, pp.3443~3457 (2006)
- Otake, Y, "Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA", Blood, 109, pp.3069~3075 (2007)
- Kaelin, Jr, "The concept of synthetic lethality in the context of anticancer therapy", Nat. Rev. Cancer, 5, pp.689~698 (2005)
- Chan, D. A, "Targeting cancer cells by synthetic lethality: autophagy and VHL in cancer therapeutics", Cell Cycle, 7, pp.2987~2990 (2008)
- Bommi-Reddy, A, "Slaying RAS with a synthetic lethal weapon", Cell Res, 20, pp.119~121 (2010)
- Kaelin, Jr. W. G, "Synthetic lethality: a framework for the development of wiser cancer therapeutics", Genome Med, 1, pp.99~ (2009)
- Wang, Y. A, "Differential enhancement of the anti-cancer effect of doxorubicin by Akt inhibitors on human breast cancer cells with differing genetic backgrounds", Oncol. Rep, 21, pp.437~442 (2009)
