Deguelin analogue SH-1242 inhibits Hsp90 activity and exerts potent anticancer efficacy with limited neurotoxicity

Cancer Research

Volumn 76, Issue 3, 2016, Pages 686-699

  Lee, Su Chan ^a   Min, Hye Young ^a   Choi, Hoon ^a   Bae, Song Yi ^a   Park, Kwan Hee ^a   Hyun, Seung Yeob ^a   Lee, Ho Jin ^a   Moon, Jayoung ^a   Park, Shin Hyung ^a   Kim, Jun Yong ^b   An, Hongchan ^a   Park, So Jung ^c   Seo, Ji Hae ^a   Lee, Seungbeom ^a   Kim, Young Myeong ^d   Park, Hyun Ju ^c   Lee, Sang Kook ^a   Lee, Jeewoo ^a   Lee, Jeeyeon ^a   Kim, Kyu Won ^a,b   Suh, Young Ger ^a   Lee, Ho Young ^a   more..

^a Seoul National University   (South Korea)

^b Seoul National University   (South Korea)

^c Sungkyunkwan University   (South Korea)

^d Kangwon National University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CASPASE 3; CD31 ANTIGEN; DEGUELIN; GELDANAMYCIN; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; K RAS PROTEIN; SH 1242; TANESPIMYCIN; UNCLASSIFIED DRUG; 2-(3,4-DIMETHOXYPHENYL)-1-(5-METHOXY-2,2-DIMETHYL-2H-CHROMEN-6-YL)ETHANONE; ANTINEOPLASTIC AGENT; BENZOPYRAN DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE RESPONSE; DOWN REGULATION; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SCREENING; EFFECTIVE DOSE (PHARMACOLOGY); GENE MUTATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER; MOLECULAR DOCKING; MOUSE; NEUROTOXICITY; NONHUMAN; ONCOGENE K RAS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; RAT; TUMOR VOLUME; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; DRUG EFFECTS; METABOLISM; SPRAGUE DAWLEY RAT; TRANSGENIC MOUSE; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZOPYRANS; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG SCREENING ASSAYS, ANTITUMOR; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MICE; MICE, TRANSGENIC; RATS; RATS, SPRAGUE-DAWLEY; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84958171100     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-15-1492     Document Type: Article

References (50)

1. Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 2010;10:537-49.
2. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005;5:761-72.
3. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100: 57-70.
4. Sawai A, Chandarlapaty S, Greulich H, Gonen M, Ye Q, Arteaga CL, et al. Inhibition of Hsp90 down-regulates mutant epidermal growth factor receptor (EGFR) expression and sensitizes EGFR mutant tumors to paclitaxel. Cancer Res 2008;68:589-96.
5. Bao R, Lai CJ, Wang DG, Qu H, Yin L, Zifcak B, et al. Targeting heat shock protein 90 with CUDC-305 overcomes erlotinib resistance in non-small cell lung cancer. Mol Cancer Ther 2009;8:3296-306.
6. Wainberg ZA, Anghel A, Rogers AM, Desai AJ, Kalous O, Conklin D, et al. Inhibition of HSP90 with AUY922 induces synergy in HER2-Amplified trastuzumab-resistant breast and gastric cancer. Mol Cancer Ther 2013;12: 509-19.
7. Schulte TW, Akinaga S, Soga S, Sullivan W, Stensgard B, Toft D, et al. Antibiotic radicicol binds to the N-Terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 1998;3:100-8.
8. Garcia-Carbonero R, Carnero A, Paz-Ares L. Inhibition of HSP90 molecular chaperones: moving into the clinic. Lancet Oncol 2013;14:e358-69.
9. Erlichman C. Tanespimycin: The opportunities and challenges of targeting heat shock protein 90. Expert Opin Investig Drugs 2009;18:861-8.
10. McCollum AK, Teneyck CJ, Sauer BM, Toft DO,Erlichman C. Up-regulation of heat shock protein 27 induces resistance to 17-Allylamino-demethoxygeldanamycin through a glutathione-mediated mechanism. Cancer Res 2006;66:10967-75.
11. Burlison JA, Neckers L, Smith AB, Maxwell A, Blagg BS. Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90. J Am Chem Soc 2006;128:15529-36.
12. Itoh H, Ogura M, Komatsuda A, Wakui H, Miura AB, Tashima Y. A novel chaperone-Activity-reducing mechanism of the 90-kDa molecular chaperone HSP90. Biochem J 1999;343 Pt 3:697-703.
13. Georgakis GV, Younes A. Heat-shock protein 90 inhibitors in cancer therapy: 17AAG and beyond. Future Oncol 2005;1:273-81.
14. Kusuma BR, Khandelwal A, Gu W, Brown D, Liu W, Vielhauer G, et al. Synthesis and biological evaluation of coumarin replacements of novobiocin as Hsp90 inhibitors. Bioorg Med Chem 2014;22:1441-9.
15. Sidera K, Patsavoudi E. HSP90 inhibitors: current development and potential in cancer therapy. Recent Pat Anticancer Drug Discov 2014;9:1-20.
16. Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: Are we there yet? Clin Cancer Res 2012;18:64-76.
17. Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012;75:311-35.
18. Suh YA, Kim JH, SungMA, Boo HJ, Yun HJ, Lee SH, et al. A novel antitumor activity of deguelin targeting the insulin-like growth factor (IGF) receptor pathway via up-regulation of IGF-binding protein-3 expression in breast cancer. Cancer Lett 2013;332:102-9.
19. Udeani GO, Gerhauser C, Thomas CF, Moon RC, Kosmeder JW, Kinghorn AD, et al. Cancer chemopreventive activity mediated by deguelin, a naturally occurring rotenoid. Cancer Res 1997;57:3424-8.
20. Chun KH, Kosmeder JW II, Sun S, Pezzuto JM, Lotan R, Hong WK, et al. Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells. J Natl Cancer Inst 2003;95:291-302.
21. Lee HY, Oh SH, Woo JK, Kim WY, Van Pelt CS, Price RE, et al. Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis. J Natl Cancer Inst 2005;97:1695-9.
22. Woo JK, Choi DS, Tran HT, Gilbert BE, Hong WK, Lee HY. Liposomal encapsulation of deguelin: evidence for enhanced antitumor activity in tobacco carcinogen-induced and oncogenic K-ras-induced lung tumorigenesis. Cancer Prev Res 2009;2:361-9.
23. Oh SH, Woo JK, Jin Q, Kang HJ, Jeong JW, Kim KW, et al. Identification of novel antiangiogenic anticancer activities of deguelin targeting hypoxiainducible factor-1 alpha. Int J Cancer 2008;122:5-14.
24. Oh SH, Woo JK, Yazici YD, Myers JN, Kim WY, Jin Q, et al. Structural basis for depletion of heat shock protein 90 client proteins by deguelin. J Natl Cancer Inst 2007;99:949-61.
25. Chang DJ, An H, Kim KS, Kim HH, Jung J, Lee JM, et al. Design, synthesis, and biological evaluation of novel deguelin-based heat shock protein 90 (HSP90) inhibitors targeting proliferation and angiogenesis. J Med Chem 2012;55:10863-84.
26. Jo DH, An H, Chang DJ, Baek YY, Cho CS, Jun HO, et al. Hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retina is suppressed by HIF-1alpha destabilization by SH-1242 and SH-1280, novel hsp90 inhibitors. J Mol Med 2014;92:1083-92.
27. Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxid Redox Signal 2008;10:1343-74.
28. Xu H, Li X, Ding W, Zeng X, Kong H, Wang H, et al. Deguelin induces the apoptosis of lung cancer cells through regulating a ROS driven Akt pathway. Cancer Cell Int 2015;15:25.
29. Taipale M, Jarosz DF, Lindquist S. HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol 2010;11: 515-28.
30. ScaltritiM, Dawood S, Cortes J. Molecular pathways: Targeting hsp90-who benefits and who does not. Clin Cancer Res 2012;18:4508-13.
31. Yadav V, Zhang X, Liu J, Estrem S, Li S, Gong XQ, et al. Reactivation of mitogen-Activated protein kinase (MAPK) pathway by FGF receptor 3 (FGFR3)/Ras mediates resistance to vemurafenib in human B-RAF V600E mutant melanoma. J Biol Chem 2012;287:28087-98.
32. Kim WY, Prudkin L, Feng L, Kim ES, Hennessy B, Lee JS, et al. Epidermal growth factor receptor and K-Rasmutations and resistance of lung cancer to insulin-like growth factor 1 receptor tyrosine kinase inhibitors. Cancer 2012;118:3993-4003.
33. Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000;21:505-15.
34. Zhang W, Huang P. Cancer-stromal interactions: role in cell survival, metabolism and drug sensitivity. Cancer Biol Ther 2011;11:150-6.
35. Johnson L, Mercer K, GreenbaumD, Bronson RT, Crowley D, Tuveson DA, et al. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 2001;410:1111-6.
36. Clapper ML, Hensley HH, Chang WC, Devarajan K, Nguyen MT, Cooper HS.Detection of colorectal adenomas using a bioactivatable probe specific for matrix metalloproteinase activity. Neoplasia 2011;13:685-91.
37. Caboni P, Sherer TB, Zhang N, Taylor G, Na HM, Greenamyre JT, et al. Rotenone, deguelin, their metabolites, and the rat model of Parkinson's disease. Chem Res Toxicol 2004;17:1540-8.
38. Jhaveri K, Taldone T, Modi S, Chiosis G. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochim Biophys Acta 2012;1823:742-55.
39. Katschinski DM, Le L, Schindler SG, Thomas T, Voss AK, Wenger RH. Interaction of the PAS B domain with HSP90 accelerates hypoxia-inducible factor-1alpha stabilization. Cell Physiol Biochem 2004;14:351-60.
40. Minet E, Mottet D, Michel G, Roland I, Raes M, Remacle J, et al. Hypoxiainduced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction. FEBS Lett 1999;460:251-6.
41. Zhou J, Schmid T, Frank R, Brune B. PI3K/Akt is required for heat shock proteins to protect hypoxia-inducible factor 1alpha from pVHL-independent degradation. J Biol Chem 2004;279:13506-13.
42. Isaacs JS, Jung Y-J, Neckers L. Aryl hydrocarbon nuclear translocator (ARNT) promotes oxygen-independent stabilization of hypoxia-inducible factor-1{alpha} by modulating an Hsp90-dependent regulatory pathway. J Biol Chem 2004;279:16128-35.
43. Soti C, Racz A, Csermely P. A Nucleotide-dependent molecular switch controls ATP binding at the C-Terminal domain of Hsp90. N-Terminal nucleotide binding unmasks a C-Terminal binding pocket. J Biol Chem 2002;277:7066-75.
44. Marcu MG, Chadli A, Bouhouche I, Catelli M, Neckers LM. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J Biol Chem 2000;275:37181-6.
45. Garnier C, Lafitte D, Tsvetkov PO, Barbier P, Leclerc-Devin J, Millot JM, et al. Binding of ATP to heat shock protein 90: evidence for an ATP-binding site in the C-Terminal domain. J Biol Chem 2002;277:12208-14.
46. Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, et al. Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 2000;101: 199-210.
47. Kitson RR, Moody CJ. Learning from nature: Advances in geldanamycin-And radicicol-based inhibitors of Hsp90. J Org Chem 2013;78: 5117-41.
48. Sgobba M, Degliesposti G, Ferrari AM, Rastelli G. Structural models and binding site prediction of the C-Terminal domain of human Hsp90: A new target for anticancer drugs. Chem Biol Drug Des 2008; 71:420-33.
49. Lee SC, Min HY, Choi H, Kim HS, Kim KC, Park SJ, et al. Synthesis and evaluation of a novel deguelin derivative, L80, which disrupts ATP binding to the C-Terminal domain of heat shock protein 90. Mol Pharmacol 2015;88:245-55.
50. Moroni E, Zhao H, Blagg BS, Colombo G. Exploiting conformational dynamics in drug discovery: design of C-Terminal inhibitors of Hsp90 with improved activities. J Chem Inf Model 2014;54:195-208.