Skip to main content
Top
Published in: Tumor Biology 2/2014

01-02-2014 | Research Article

Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation

Authors: Gang He, Yan Wang, Xueli Pang, Bo Zhang

Published in: Tumor Biology | Issue 2/2014

Login to get access

Abstract

Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Liu S et al. Randomized, controlled phase II study of post-surgery radiotherapy combined with recombinant adenoviral human p53 gene therapy in treatment of oral cancer. Canc Gene Ther. 2013;20(6):375–8.CrossRef Liu S et al. Randomized, controlled phase II study of post-surgery radiotherapy combined with recombinant adenoviral human p53 gene therapy in treatment of oral cancer. Canc Gene Ther. 2013;20(6):375–8.CrossRef
2.
go back to reference Lövey J et al. Radiosensitivity of human prostate cancer cells can be modulated by inhibition of 12-lipoxygenase. Cancer Lett. 2013;335(2):495–501.PubMedCrossRef Lövey J et al. Radiosensitivity of human prostate cancer cells can be modulated by inhibition of 12-lipoxygenase. Cancer Lett. 2013;335(2):495–501.PubMedCrossRef
3.
go back to reference Benzina S et al. High-LET radiation combined with oxaliplatin induce autophagy in U-87 glioblastoma cells. Cancer Lett. 2008;264(1):63–70.PubMedCrossRef Benzina S et al. High-LET radiation combined with oxaliplatin induce autophagy in U-87 glioblastoma cells. Cancer Lett. 2008;264(1):63–70.PubMedCrossRef
4.
go back to reference Weichert W et al. Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res. 2008;14(6):1669–77.PubMedCrossRef Weichert W et al. Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res. 2008;14(6):1669–77.PubMedCrossRef
5.
go back to reference Weichert W et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 2008;9(2):139–48.PubMedCrossRef Weichert W et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 2008;9(2):139–48.PubMedCrossRef
6.
go back to reference Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett. 2009;280(2):168–76.PubMedCrossRef Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett. 2009;280(2):168–76.PubMedCrossRef
7.
go back to reference Johnstone RW. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov. 2002;1(4):287–99.PubMedCrossRef Johnstone RW. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov. 2002;1(4):287–99.PubMedCrossRef
8.
go back to reference Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5(9):769–84.PubMedCrossRef Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5(9):769–84.PubMedCrossRef
9.
go back to reference Carafa V, Nebbioso A, Altucci L. Histone deacetylase inhibitors: recent insights from basic to clinical knowledge & patenting of anti-cancer actions. Recent Pat Anticancer Drug Discov. 2011;6(1):131–45.PubMedCrossRef Carafa V, Nebbioso A, Altucci L. Histone deacetylase inhibitors: recent insights from basic to clinical knowledge & patenting of anti-cancer actions. Recent Pat Anticancer Drug Discov. 2011;6(1):131–45.PubMedCrossRef
10.
go back to reference Mottet D, Castronovo V. Histone deacetylases: anti-angiogenic targets in cancer therapy. Curr Cancer Drug Targets. 2010;10(8):898–913.PubMedCrossRef Mottet D, Castronovo V. Histone deacetylases: anti-angiogenic targets in cancer therapy. Curr Cancer Drug Targets. 2010;10(8):898–913.PubMedCrossRef
11.
go back to reference Bots M, Johnstone RW. Rational combinations using HDAC inhibitors. Clin Cancer Res. 2009;15(12):3970–7.PubMedCrossRef Bots M, Johnstone RW. Rational combinations using HDAC inhibitors. Clin Cancer Res. 2009;15(12):3970–7.PubMedCrossRef
12.
go back to reference Gore SD et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 2006;66(12):6361–9.PubMedCrossRef Gore SD et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 2006;66(12):6361–9.PubMedCrossRef
13.
go back to reference Caron C, Boyault C, Khochbin S. Regulatory cross-talk between lysine acetylation and ubiquitination: role in the control of protein stability. Bioessays. 2005;27(4):408–15.PubMedCrossRef Caron C, Boyault C, Khochbin S. Regulatory cross-talk between lysine acetylation and ubiquitination: role in the control of protein stability. Bioessays. 2005;27(4):408–15.PubMedCrossRef
14.
go back to reference Fantin VR et al. Constitutive activation of signal transducers and activators of transcription predicts vorinostat resistance in cutaneous T-cell lymphoma. Cancer Res. 2008;68(10):3785–94.PubMedCrossRef Fantin VR et al. Constitutive activation of signal transducers and activators of transcription predicts vorinostat resistance in cutaneous T-cell lymphoma. Cancer Res. 2008;68(10):3785–94.PubMedCrossRef
15.
go back to reference Oh M, Choi IK, Kwon HJ. Inhibition of histone deacetylase1 induces autophagy. Biochem Biophys Res Commun. 2008;369(4):1179–83.PubMedCrossRef Oh M, Choi IK, Kwon HJ. Inhibition of histone deacetylase1 induces autophagy. Biochem Biophys Res Commun. 2008;369(4):1179–83.PubMedCrossRef
16.
go back to reference Gammoh N et al. Role of autophagy in histone deacetylase inhibitor-induced apoptotic and nonapoptotic cell death. Proc Natl Acad Sci U S A. 2012;109(17):6561–5.PubMedCentralPubMedCrossRef Gammoh N et al. Role of autophagy in histone deacetylase inhibitor-induced apoptotic and nonapoptotic cell death. Proc Natl Acad Sci U S A. 2012;109(17):6561–5.PubMedCentralPubMedCrossRef
17.
go back to reference Cao Y, Klionsky DJ. Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res. 2007;17(10):839–49.PubMedCrossRef Cao Y, Klionsky DJ. Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res. 2007;17(10):839–49.PubMedCrossRef
18.
19.
go back to reference Berdasco M, Esteller M. Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell. 2010;19(5):698–711.PubMedCrossRef Berdasco M, Esteller M. Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell. 2010;19(5):698–711.PubMedCrossRef
20.
go back to reference Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8(4):286–98.PubMedCrossRef Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8(4):286–98.PubMedCrossRef
21.
go back to reference Liu Y, He G, Wang Y, Guan X, Pang X, Zhang B. MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells. Toxicol Lett. 2013;221(1):23–30.PubMedCrossRef Liu Y, He G, Wang Y, Guan X, Pang X, Zhang B. MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells. Toxicol Lett. 2013;221(1):23–30.PubMedCrossRef
22.
go back to reference Rhodes LV et al. The histone deacetylase inhibitor trichostatin A alters microRNA expression profiles in apoptosis-resistant breast cancer cells. Oncol Rep. 2012;27(1):10–6.PubMed Rhodes LV et al. The histone deacetylase inhibitor trichostatin A alters microRNA expression profiles in apoptosis-resistant breast cancer cells. Oncol Rep. 2012;27(1):10–6.PubMed
23.
go back to reference Frew AJ et al. Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist. Proc Natl Acad Sci U S A. 2008;105(32):11317–22.PubMedCentralPubMedCrossRef Frew AJ et al. Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist. Proc Natl Acad Sci U S A. 2008;105(32):11317–22.PubMedCentralPubMedCrossRef
24.
go back to reference Camphausen K, Tofilon PJ. Inhibition of histone deacetylation: a strategy for tumor radiosensitization. J Clin Oncol. 2007;26:4051–6.CrossRef Camphausen K, Tofilon PJ. Inhibition of histone deacetylation: a strategy for tumor radiosensitization. J Clin Oncol. 2007;26:4051–6.CrossRef
25.
go back to reference Folkvord S et al. Radiosensitization by SAHA in experimental colorectal carcinoma models—in vivo effects and relevance of histone acetylation status. Int J Radiat Oncol Biol Phys. 2009;74(2):546–52.PubMedCrossRef Folkvord S et al. Radiosensitization by SAHA in experimental colorectal carcinoma models—in vivo effects and relevance of histone acetylation status. Int J Radiat Oncol Biol Phys. 2009;74(2):546–52.PubMedCrossRef
26.
go back to reference Ree AH et al. Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: the Pelvic radiation and Vorinostat (PRAVO) phase 1 study. Lancet Oncol. 2010;11(5):459–64.PubMedCrossRef Ree AH et al. Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: the Pelvic radiation and Vorinostat (PRAVO) phase 1 study. Lancet Oncol. 2010;11(5):459–64.PubMedCrossRef
27.
go back to reference Chowdhury S et al. Histone deacetylase inhibitor belinostat represses survivin expression through reactivation of transforming growth factor beta (TGFbeta) receptor II leading to cancer cell death. J Biol Chem. 2011;286(35):30937–48.PubMedCrossRef Chowdhury S et al. Histone deacetylase inhibitor belinostat represses survivin expression through reactivation of transforming growth factor beta (TGFbeta) receptor II leading to cancer cell death. J Biol Chem. 2011;286(35):30937–48.PubMedCrossRef
28.
go back to reference Kondo Y et al. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005;5(9):726–34.PubMedCrossRef Kondo Y et al. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005;5(9):726–34.PubMedCrossRef
29.
go back to reference Livesey KM et al. Autophagy inhibition in combination cancer treatment. Curr Opin Investig Drugs. 2009;10(12):1269–79.PubMed Livesey KM et al. Autophagy inhibition in combination cancer treatment. Curr Opin Investig Drugs. 2009;10(12):1269–79.PubMed
30.
go back to reference Sy LK et al. Timosaponin A-III induces autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells. Cancer Res. 2008;68(24):10229–37.PubMedCrossRef Sy LK et al. Timosaponin A-III induces autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells. Cancer Res. 2008;68(24):10229–37.PubMedCrossRef
31.
go back to reference Akar U et al. Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy. 2008;4(5):669–79.PubMed Akar U et al. Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells. Autophagy. 2008;4(5):669–79.PubMed
32.
33.
go back to reference Dai ZJ et al. Antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy. Int J Mol Sci. 2013;14(1):273–85.PubMedCentralCrossRef Dai ZJ et al. Antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy. Int J Mol Sci. 2013;14(1):273–85.PubMedCentralCrossRef
Metadata
Title
Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation
Authors
Gang He
Yan Wang
Xueli Pang
Bo Zhang
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1134-z

Other articles of this Issue 2/2014

Tumor Biology 2/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine