Repositioning antipsychotic chlorpromazine for treating colorectal cancer by inhibiting sirtuin 1

Oncotarget

Volumn 6, Issue 29, 2015, Pages 27580-27595

  Lee, Wen Ying ^a,b   Lee, Wai Theng ^b   Cheng, Chia Hsiung ^b   Chen, Ku Chung ^b   Chou, Chih Ming ^b   Chung, Chu Hung ^c   Sun, Min Siou ^c   Cheng, Hung Wei ^b   Ho, Meng Ni ^b   Lin, Cheng Wei ^b  

^a CHI MEI MEDICAL CENTER   (Taiwan)

^b TAIPEI MEDICAL UNIVERSITY   (Taiwan)

^c INSTITUTE OF CELLULAR AND ORGANISMIC BIOLOGY   (Taiwan)

Author keywords

Apoptosis; Chlorpromazine; Drug reposition; P53; SIRT1

Indexed keywords

CHLORPROMAZINE; LYSINE; MESSENGER RNA; PROTEIN P53; SIRTUIN 1; STRESS ACTIVATED PROTEIN KINASE; ANTINEOPLASTIC AGENT; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; NEUROLEPTIC AGENT; SIRT1 PROTEIN, HUMAN; TP53 PROTEIN, HUMAN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL VIABILITY; COLORECTAL CANCER; COLORECTAL CANCER CELL LINE; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; DRUG STRUCTURE; ENZYME ACTIVATION; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PROTEIN ACETYLATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; SIRT1 GENE; TUMOR VOLUME; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CANCER TRANSPLANTATION; CELL SURVIVAL; CHEMISTRY; COLORECTAL NEOPLASMS; DNA MICROARRAY; DRUG REPOSITIONING; HCT 116 CELL LINE; HT-29 CELL LINE; METABOLISM; NONOBESE DIABETIC MOUSE; OXIDATIVE STRESS; POINT MUTATION; SCID MOUSE; TREATMENT OUTCOME; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTIPSYCHOTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; CELL SURVIVAL; CHLORPROMAZINE; COLORECTAL NEOPLASMS; DRUG REPOSITIONING; GENE EXPRESSION REGULATION, NEOPLASTIC; HCT116 CELLS; HT29 CELLS; HUMANS; MAP KINASE KINASE 4; MICE; MICE, INBRED NOD; MICE, SCID; NEOPLASM TRANSPLANTATION; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; OXIDATIVE STRESS; POINT MUTATION; SIRTUIN 1; TREATMENT OUTCOME; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84944463989     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.4768     Document Type: Article

References (52)

1. Naccarati A, Polakova V, Pardini B, Vodickova L, Hemminki K, Kumar R, Vodicka P. Mutations and polymorphisms in TP53 gene-an overview on the role in colorectal cancer. Mutagenesis. 2012; 27:211-218.
2. Muller PA, Vousden KH. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer cell. 2014; 25:304-317.
3. Shangary S, Wang S. Targeting the MDM2-p53 interaction for cancer therapy. Clin Cancer Res. 2008; 14:5318-5324.
4. Tang Y, Zhao W, Chen Y, Zhao Y, Gu W. Acetylation is indispensable for p53 activation. Cell. 2008; 133:612-626.
5. Li M, Luo J, Brooks CL, Gu W. Acetylation of p53 inhibits its ubiquitination by Mdm2. J Biol Chem. 2002; 277:50607-50611.
6. Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, Yao TP. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J. 2002; 21:6236-6245.
7. van Leeuwen IM, Higgins M, Campbell J, McCarthy AR, Sachweh MC, Navarro AM, Lain S. Modulation of p53 C-terminal acetylation by mdm2, p14ARF, and cytoplasmic SirT2. Mol Cancer Ther. 2013; 12:471-480.
8. Muller BM, Jana L, Kasajima A, Lehmann A, Prinzler J, Budczies J, Winzer KJ, Dietel M, Weichert W, Denkert C. Differential expression of histone deacetylases HDAC1, 2 and 3 in human breast cancer-overexpression of HDAC2 and HDAC3 is associated with clinicopathological indicators of disease progression. BMC Cancer. 2013; 13:215.
9. Chen X, Sun K, Jiao S, Cai N, Zhao X, Zou H, Xie Y, Wang Z, Zhong M, Wei L. High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients. Sci Rep. 2014; 4:7481.
10. Yu Q, Li Y, Mu K, Li Z, Meng Q, Wu X, Wang Y, Li L. Amplification of Mdmx and overexpression of MDM2 contribute to mammary carcinogenesis by substituting for p53 mutations. Diagn Pathol. 2014; 9:71.
11. Hoffmann G, Breitenbucher F, Schuler M, Ehrenhofer-Murray AE. A novel sirtuin 2 (SIRT2) inhibitor with p53-dependent pro-apoptotic activity in non-small cell lung cancer. J Biol Chem. 2014; 289:5208-5216.
12. Peck B, Chen CY, Ho KK, Di Fruscia P, Myatt SS, Coombes RC, Fuchter MJ, Hsiao CD, Lam EW. SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol Cancer Ther. 2010; 9:844-855.
13. Wang J, Kim TH, Ahn MY, Lee J, Jung JH, Choi WS, Lee BM, Yoon KS, Yoon S, Kim HS. Sirtinol, a class III HDAC inhibitor, induces apoptotic and autophagic cell death in MCF-7 human breast cancer cells. Int J Oncol. 2012; 41:1101-1109.
14. Blagosklonny MV. A new science-business paradigm in anticancer drug development. Trends Biotechnol. 2003; 21:103-106.
15. Mohammed A, Janakiram NB, Madka V, Brewer M, Ritchie RL, Lightfoot S, Kumar G, Sadeghi M, Patlolla JM, Yamada HY, Cruz-Monserrate Z, May R, Houchen CW, Steele VE, Rao CV. Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression. Oncotarget. 2015.
16. Zhu Y, Casey PJ, Kumar AP, Pervaiz S. Deciphering the signaling networks underlying simvastatin-induced apoptosis in human cancer cells: evidence for non-canonical activation of RhoA and Rac1 GTPases. Cell death & disease. 2013; 4:e568.
17. Babcook MA, Shukla S, Fu P, Vazquez EJ, Puchowicz MA, Molter JP, Oak CZ, MacLennan GT, Flask CA, Lindner DJ, Parker Y, Daneshgari F, Gupta S. Synergistic simvastatin and metformin combination chemotherapy for osseous metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2014; 13:2288-2302.
18. Vainio P, Lehtinen L, Mirtti T, Hilvo M, Seppanen-Laakso T, Virtanen J, Sankila A, Nordling S, Lundin J, Rannikko A, Oresic M, Kallioniemi O, Iljin K. Phospholipase PLAG7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins. Oncotarget. 2011; 2:1176-1190.
19. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009; 69:7507-7511.
20. Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat. 2011; 126:355-364.
21. Del Barco S, Vazquez-Martin A, Cufi S, Oliveras-Ferraros C, Bosch-Barrera J, Joven J, Martin-Castillo B, Menendez JA. Metformin: multi-faceted protection against cancer. Oncotarget. 2011; 2:896-917.
22. Gritti M, Wurth R, Angelini M, Barbieri F, Peretti M, Pizzi E, Pattarozzi A, Carra E, Sirito R, Daga A, Curmi PM, Mazzanti M, Florio T. Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current. Oncotarget. 2014; 5:11252-11268.
23. Chen MH, Yang WL, Lin KT, Liu CH, Liu YW, Huang KW, Chang PM, Lai JM, Hsu CN, Chao KM, Kao CY, Huang CY. Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma. PloS one. 2011; 6:e27186.
24. Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, Reich M, Hieronymus H, Wei G, Armstrong SA, Haggarty SJ, Clemons PA, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006; 313:1929-1935.
25. Shin SY, Kim CG, Kim SH, Kim YS, Lim Y, Lee YH. Chlorpromazine activates p21Waf1/Cip1 gene transcription via early growth response-1 (Egr-1) in C6 glioma cells. Exp Mol Med. 2010; 42:395-405.
26. Shin SY, Lee KS, Choi YK, Lim HJ, Lee HG, Lim Y, Lee YH. The antipsychotic agent chlorpromazine induces autophagic cell death by inhibiting the Akt/mTOR pathway in human U-87MG glioma cells. Carcinogenesis. 2013; 34:2080-2089.
27. Wu GS. The functional interactions between the p5 and MAPK signaling pathways. Cancer biology & therapy. 2004; 3:156-161.
28. Li D, Marchenko ND, Moll UM. SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis. Cell Death Differ. 2011; 18:1904-1913.
29. Zhang Y, Zhang Q, Zeng SX, Mayo LD, Lu H. Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth. Cancer biology & therapy. 2012; 13:915-924.
30. Kawano T, Akiyama M, Agawa-Ohta M, Mikami-Terao Y, Iwase S, Yanagisawa T, Ida H, Agata N, Yamada H. Histone deacetylase inhibitors valproic acid and depsipeptide sensitize retinoblastoma cells to radiotherapy by increasing H2AX phosphorylation and p53 acetylation-phosphorylation. Int J Oncol. 2010; 37:787-795.
31. Yde CW, Clausen MP, Bennetzen MV, Lykkesfeldt AE, Mouritsen OG, Guerra B. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells. Anticancer Drugs. 2009; 20:723-735.
32. Stenzinger A, Endris V, Klauschen F, Sinn B, Lorenz K, Warth A, Goeppert B, Ehemann V, Muckenhuber A, Kamphues C, Bahra M, Neuhaus P, Weichert W. High SIRT1 expression is a negative prognosticator in pancreatic ductal adenocarcinoma. BMC Cancer. 2013; 13:450.
33. Jung-Hynes B, Nihal M, Zhong W, Ahmad N. Role of sirtuin histone deacetylase SIRT1 in prostate cancer. A target for prostate cancer management via its inhibition? J Biol Chem. 2009; 284:3823-3832.
34. Elangovan S, Ramachandran S, Venkatesan N, Ananth S, Gnana-Prakasam JP, Martin PM, Browning DD, Schoenlein PV, Prasad PD, Ganapathy V, Thangaraju M. SIRT1 is essential for oncogenic signaling by estrogen/estrogen receptor alpha in breast cancer. Cancer Res. 2011; 71:6654-6664.
35. Portmann S, Fahrner R, Lechleiter A, Keogh A, Overney S, Laemmle A, Mikami K, Montani M, Tschan MP, Candinas D, Stroka D. Antitumor effect of SIRT1 inhibition in human HCC tumor models in vitro and in vivo. Mol Cancer Ther. 2013; 12:499-508.
36. Wang C, Chen L, Hou X, Li Z, Kabra N, Ma Y, Nemoto S, Finkel T, Gu W, Cress WD, Chen J. Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006; 8:1025-1031.
37. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004; 303:2011-2015.
38. Zhang Q, Zeng SX, Zhang Y, Ding D, Ye Q, Meroueh SO, Lu H. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med. 2012; 4:298-312.
39. Lain S, Hollick JJ, Campbell J, Staples OD, Higgins M, Aoubala M, McCarthy A, Appleyard V, Murray KE, Baker L, Thompson A, Mathers J, Holland SJ, Stark MJ, Pass G, Woods J, et al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer cell. 2008; 13:454-463.
40. Zhang Y, Zhang Q, Zeng SX, Hao Q, Lu H. Inauhzin sensitizes p53-dependent cytotoxicity and tumor suppression of chemotherapeutic agents. Neoplasia. 2013; 15:523-534.
41. Li L, Wang L, Wang Z, Ho Y, McDonald T, Holyoake TL, Chen W, Bhatia R. Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib. Cancer cell. 2012; 21:266-281.
42. Liang Z, Yang Y, Wang H, Yi W, Yan X, Yan J, Li Y, Feng Y, Yu S, Yang J, Jin Z, Duan W, Chen W. Inhibition of SIRT1 signaling sensitizes the antitumor activity of silybin against human lung adenocarcinoma cells in vitro and in vivo. Mol Cancer Ther. 2014; 13:1860-1872.
43. Yamaguchi H, Woods NT, Piluso LG, Lee HH, Chen J, Bhalla KN, Monteiro A, Liu X, Hung MC, Wang HG. p53 acetylation is crucial for its transcription-independent proapoptotic functions. J Biol Chem. 2009; 284:11171-11183.
44. Yang Y, Fu W, Chen J, Olashaw N, Zhang X, Nicosia SV, Bhalla K, Bai W. SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress. Nat Cell Biol. 2007; 9:1253-1262.
45. Sasaki T, Maier B, Koclega KD, Chruszcz M, Gluba W, Stukenberg PT, Minor W, Scrable H. Phosphorylation regulates SIRT1 function. PloS one. 2008; 3:e4020.
46. Lee CW, Wong LL, Tse EY, Liu HF, Leong VY, Lee JM, Hardie DG, Ng IO, Ching YP. AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res. 2012; 72:4394-4404.
47. Lau AW, Liu P, Inuzuka H, Gao D. SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation. Am J Cancer Res. 2014; 4:245-255.
48. Gao Z, Zhang J, Kheterpal I, Kennedy N, Davis RJ, Ye J. Sirtuin 1 (SIRT1) protein degradation in response to persistent c-Jun N-terminal kinase 1 (JNK1) activation contributes to hepatic steatosis in obesity. J Biol Chem. 2011; 286:22227-22234.
49. Nasrin N, Kaushik VK, Fortier E, Wall D, Pearson KJ, de Cabo R, Bordone L. JNK1 phosphorylates SIRT1 and promotes its enzymatic activity. PloS one. 2009; 4:e8414.
50. Lin CW, Liao MY, Lin WW, Wang YP, Lu TY, Wu HC. Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer. J Biol Chem. 2012; 287:39449-39459.
51. Jorissen RN, Gibbs P, Christie M, Prakash S, Lipton L, Desai J, Kerr D, Aaltonen LA, Arango D, Kruhoffer M, Orntoft TF, Andersen CL, Gruidl M, Kamath VP, Eschrich S, Yeatman TJ, et al. Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage, B, and C Colorectal Cancer. Clin Cancer Res. 2009; 15:7642-7651.
52. Smith JJ, Deane NG, Wu F, Merchant NB, Zhang B, Jiang A, Lu P, Johnson JC, Schmidt C, Bailey CE, Eschrich S, Kis C, Levy S, Washington MK, Heslin MJ, Coffey RJ, et al. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology. 2010; 138:958-968.