Skip to main content
SpringerLink
Log in

Heat Shock Factor 1 and Its Small Molecule Modulators with Therapeutic Potential

  • Chapter
  • First Online:
Heat Shock Proteins in Inflammatory Diseases

Part of the book series: Heat Shock Proteins ((HESP,volume 22))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

DBD:

DNA binding domain

HSE:

heat shock element

HSF1:

heat shock factor 1

HSP:

heat shock protein

HSR:

heat shock response

RD:

regulatory domain

TAD:

trans activation domain

References

  1. Ritossa F (1962) A new puffing pattern induced by temperature shock and DNP in drosophila. Experientia. https://doi.org/10.1007/BF02172188

  2. Ritossa F (1996) Discovery of the heat shock response. Cell Stress Chaperones 1:97–98. https://doi.org/10.1379/1466-1268(1996)001<0097:dothsr>2.3.co;2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Anckar J, Sistonen L (2011) Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem 80:1089–1115. https://doi.org/10.1146/annurev-biochem-060809-095203

    Article  CAS  PubMed  Google Scholar 

  4. Zimarino V, Wu C (1987) Induction of sequence-specific binding of Drosophila heat shock activator protein without protein synthesis. Nature 327:727–730. https://doi.org/10.1038/327727a0

    Article  CAS  PubMed  Google Scholar 

  5. Gomez-Pastor R, Burchfiel ET, Thiele DJ (2018) Regulation of heat shock transcription factors and their roles in physiology and disease. Nat Rev Mol Cell Biol 19:4–19. https://doi.org/10.1038/nrm.2017.73

    Article  CAS  PubMed  Google Scholar 

  6. Shi Y, Mosser DD, Morimoto RI (1998) Molecular chaperones as HSF1-specific transcriptional repressors. Genes Dev 12:654–666. https://doi.org/10.1101/gad.12.5.654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Neef DW et al (2014) A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell Rep 9:955–966. https://doi.org/10.1016/j.celrep.2014.09.056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dayalan Naidu S, Dinkova-Kostova AT (2017) Regulation of the mammalian heat shock factor 1. FEBS J 284:1606–1627. https://doi.org/10.1111/febs.13999

    Article  CAS  PubMed  Google Scholar 

  9. Vihervaara A, Sistonen L (2014) HSF1 at a glance. J Cell Sci 127:261–266. https://doi.org/10.1242/jcs.132605

    Article  CAS  PubMed  Google Scholar 

  10. Littlefield O, Nelson HC (1999) A new use for the ‘wing’ of the ‘winged’ helix-turn-helix motif in the HSF-DNA cocrystal. Nat Struct Biol 6:464–470. https://doi.org/10.1038/8269

    Article  CAS  PubMed  Google Scholar 

  11. Peteranderl R et al (1999) Biochemical and biophysical characterization of the trimerization domain from the heat shock transcription factor. Biochemistry 38:3559–3569. https://doi.org/10.1021/bi981774j

    Article  CAS  PubMed  Google Scholar 

  12. Rabindran SK, Haroun RI, Clos J, Wisniewski J, Wu C (1993) Regulation of heat shock factor trimer formation: role of a conserved leucine zipper. Science 259:230–234. https://doi.org/10.1126/science.8421783

    Article  CAS  PubMed  Google Scholar 

  13. Newton EM, Knauf U, Green M, Kingston RE (1996) The regulatory domain of human heat shock factor 1 is sufficient to sense heat stress. Mol Cell Biol 16:839–846. https://doi.org/10.1128/mcb.16.3.839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Corey LL, Weirich CS, Benjamin IJ, Kingston RE (2003) Localized recruitment of a chromatin-remodeling activity by an activator in vivo drives transcriptional elongation. Genes Dev 17:1392–1401. https://doi.org/10.1101/gad.1071803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sullivan EK, Weirich CS, Guyon JR, Sif S, Kingston RE (2001) Transcriptional activation domains of human heat shock factor 1 recruit human SWI/SNF. Mol Cell Biol 21:5826–5837. https://doi.org/10.1128/mcb.21.17.5826-5837.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Brown SA, Weirich CS, Newton EM, Kingston RE (1998) Transcriptional activation domains stimulate initiation and elongation at different times and via different residues. EMBO J 17:3146–3154. https://doi.org/10.1093/emboj/17.11.3146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Green M, Schuetz TJ, Sullivan EK, Kingston RE (1995) A heat shock-responsive domain of human HSF1 that regulates transcription activation domain function. Mol Cell Biol 15:3354–3362. https://doi.org/10.1128/mcb.15.6.3354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Guettouche T, Boellmann F, Lane WS, Voellmy R (2005) Analysis of phosphorylation of human heat shock factor 1 in cells experiencing a stress. BMC Biochem 6:4–4. https://doi.org/10.1186/1471-2091-6-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dai C (2018) The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis. Philos Trans R Soc Lond Ser B Biol Sci 373:20160525. https://doi.org/10.1098/rstb.2016.0525

    Article  CAS  Google Scholar 

  20. Hietakangas V et al (2006) PDSM, a motif for phosphorylation-dependent SUMO modification. Proc Natl Acad Sci U S A 103:45–50. https://doi.org/10.1073/pnas.0503698102

    Article  CAS  PubMed  Google Scholar 

  21. Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI (2009) Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323:1063–1066. https://doi.org/10.1126/science.1165946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kourtis N et al (2015) FBXW7 modulates cellular stress response and metastatic potential through ​HSF1 post-translational modification. Nat Cell Biol 17:322–332. https://doi.org/10.1038/ncb3121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Auluck PK, Chan HYE, Trojanowski JQ, Lee VMY, Bonini NM (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson’s disease. Science 295:865–868. https://doi.org/10.1126/science.1067389

    Article  CAS  PubMed  Google Scholar 

  24. Kim E et al (2016) NEDD4-mediated HSF1 degradation underlies α-synucleinopathy. Hum Mol Genet 25:211–222. https://doi.org/10.1093/hmg/ddv445

    Article  CAS  PubMed  Google Scholar 

  25. Donmez G et al (2012) SIRT1 protects against α-Synuclein aggregation by activating molecular chaperones. J Neurosci 32:124–132. https://doi.org/10.1523/jneurosci.3442-11.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen H-J et al (2016) The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis. Brain 139:1417–1432. https://doi.org/10.1093/brain/aww028

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kalmar B, Greensmith L (2017) Cellular chaperones as therapeutic targets in ALS to restore protein homeostasis and improve cellular function. Front Mol Neurosci 10:251–251. https://doi.org/10.3389/fnmol.2017.00251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mavroudis IA et al (2010) Morphological changes of the human purkinje cells and deposition of neuritic plaques and neurofibrillary tangles on the cerebellar cortex of Alzheimer’s disease. Am J Alzheimers Dis Other Dement 25:585–591. https://doi.org/10.1177/1533317510382892

    Article  Google Scholar 

  29. Chen Y et al (2014) Hsp90 chaperone inhibitor 17-AAG attenuates Aβ-induced synaptic toxicity and memory impairment. J Neurosci 34:2464–2470. https://doi.org/10.1523/JNEUROSCI.0151-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bobkova NV et al (2014) Therapeutic effect of exogenous hsp70 in mouse models of Alzheimer’s disease. J Alzheimers Dis 38:425–435. https://doi.org/10.3233/JAD-130779

    Article  PubMed  Google Scholar 

  31. Neef DW, Jaeger AM, Thiele DJ (2011) Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat Rev Drug Discov 10:930–944. https://doi.org/10.1038/nrd3453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Fujimoto M et al (2005) Active HSF1 significantly suppresses polyglutamine aggregate formation in cellular and mouse models. J Biol Chem 280:34908–34916. https://doi.org/10.1074/jbc.M506288200

    Article  CAS  PubMed  Google Scholar 

  33. Kondo N et al (2013) Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration. Nat Commun 4:1405–1405. https://doi.org/10.1038/ncomms2417

    Article  CAS  PubMed  Google Scholar 

  34. Dai C, Sampson SB (2016) HSF1: Guardian of Proteostasis in Cancer. Trends Cell Biol 26:17–28. https://doi.org/10.1016/j.tcb.2015.10.011

    Article  CAS  PubMed  Google Scholar 

  35. Mendillo ML et al (2012) HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell 150:549–562. https://doi.org/10.1016/j.cell.2012.06.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Santagata S et al (2011) High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer. Proc Natl Acad Sci U S A 108:18378–18383. https://doi.org/10.1073/pnas.1115031108

    Article  PubMed  PubMed Central  Google Scholar 

  37. Dai C et al (2012) Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis. J Clin Invest 122:3742–3754. https://doi.org/10.1172/jci62727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tang Z et al (2015) MEK guards proteome stability and inhibits tumor-suppressive amyloidogenesis via HSF1. Cell 160:729–744. https://doi.org/10.1016/j.cell.2015.01.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hu Y, Mivechi NF (2011) Promotion of heat shock factor Hsf1 degradation via adaptor protein filamin A-interacting protein 1-like (FILIP-1L). J Biol Chem 286:31397–31408. https://doi.org/10.1074/jbc.M111.255851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kwon M, Libutti SK (2014) Filamin a interacting protein 1-like as a therapeutic target in cancer. Expert Opin Ther Targets 18:1435–1447. https://doi.org/10.1517/14728222.2014.957181

    Article  CAS  PubMed  Google Scholar 

  41. Meng L, Gabai VL, Sherman MY (2010) Heat-shock transcription factor HSF1 has a critical role in human epidermal growth factor receptor-2-induced cellular transformation and tumorigenesis. Oncogene 29:5204–5213. https://doi.org/10.1038/onc.2010.277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Dai C et al (2012) Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis. J Clin Invest 122:3742–3754. https://doi.org/10.1172/JCI62727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jin X, Moskophidis D, Hu Y, Phillips A, Mivechi NF (2009) Heat shock factor 1 deficiency via its downstream target gene alphaB-crystallin (Hspb5) impairs p53 degradation. J Cell Biochem 107:504–515. https://doi.org/10.1002/jcb.22151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Su K-H et al (2016) HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and promote growth. Nat Cell Biol 18:527–539. https://doi.org/10.1038/ncb3335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Westerheide SD, Morimoto RI (2005) Heat shock response modulators as therapeutic tools for diseases of protein conformation. J Biol Chem 280:33097–33100. https://doi.org/10.1074/jbc.R500010200

    Article  CAS  PubMed  Google Scholar 

  46. Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C (2001) Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer’s disease. Prog Neuro-Psychopharmacol Biol Psychiatry 25:1341–1357. https://doi.org/10.1016/s0278-5846(01)00192-0

    Article  CAS  Google Scholar 

  47. Westerheide SD et al (2004) Celastrols as inducers of the heat shock response and cytoprotection. J Biol Chem 279:56053–56060. https://doi.org/10.1074/jbc.M409267200

    Article  CAS  PubMed  Google Scholar 

  48. Zhang T et al (2008) A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. Mol Cancer Ther 7:162–170. https://doi.org/10.1158/1535-7163.MCT-07-0484

    Article  CAS  PubMed  Google Scholar 

  49. Cleren C, Calingasan NY, Chen J, Beal MF (2005) Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity. J Neurochem 94:995–1004. https://doi.org/10.1111/j.1471-4159.2005.03253.x

    Article  CAS  PubMed  Google Scholar 

  50. Subapriya R, Nagini S (2005) Medicinal properties of neem leaves: a review. Curr Med Chem Anticancer Agents 5:149–146

    Article  CAS  Google Scholar 

  51. Misra S et al (2011) Gedunin and photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host. Parasitol Res 109:1351–1360. https://doi.org/10.1007/s00436-011-2380-x

    Article  PubMed  Google Scholar 

  52. Brandt GE, Schmidt MD, Prisinzano TE, Blagg BS (2008) Gedunin, a novel hsp90 inhibitor: semisynthesis of derivatives and preliminary structure-activity relationships. J Med Chem 51:6495–6502. https://doi.org/10.1021/jm8007486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Patwardhan CA et al (2013) Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis. J Biol Chem 288:7313–7325. https://doi.org/10.1074/jbc.M112.427328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang X, Timmermann B, Samadi AK, Cohen MS (2012) Withaferin a induces proteasome-dependent degradation of breast cancer susceptibility gene 1 and heat shock factor 1 proteins in breast cancer cells. ISRN Biochem 2012:707586. https://doi.org/10.5402/2012/707586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Santagata S et al (2012) Using the heat-shock response to discover anticancer compounds that target protein homeostasis. ACS Chem Biol 7:340–349. https://doi.org/10.1021/cb200353m

    Article  CAS  PubMed  Google Scholar 

  56. Yu Y et al (2010) Withaferin a targets heat shock protein 90 in pancreatic cancer cells. Biochem Pharmacol 79:542–551. https://doi.org/10.1016/j.bcp.2009.09.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Marathe SA, Dasgupta I, Gnanadhas DP, Chakravortty D (2011) Multifaceted roles of curcumin: two sides of a coin! Expert Opin Biol Ther 11:1485–1499. https://doi.org/10.1517/14712598.2011.623124

    Article  CAS  PubMed  Google Scholar 

  58. Teiten MH, Reuter S, Schmucker S, Dicato M, Diederich M (2009) Induction of heat shock response by curcumin in human leukemia cells. Cancer Lett 279:145–154. https://doi.org/10.1016/j.canlet.2009.01.031

    Article  CAS  PubMed  Google Scholar 

  59. Hamaguchi T, Ono K, Yamada M (2010) REVIEW: Curcumin and Alzheimer’s disease. CNS Neurosci Ther 16:285–297. https://doi.org/10.1111/j.1755-5949.2010.00147.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang Y, Kensler TW, Cho CG, Posner GH, Talalay P (1994) Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci U S A 91:3147–3150. https://doi.org/10.1073/pnas.91.8.3147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhang J et al (2017) Beneficial effects of Sulforaphane treatment in Alzheimer’s disease may be mediated through reduced HDAC1/3 and increased P75NTR expression. Front Aging Neurosci 9:121–121. https://doi.org/10.3389/fnagi.2017.00121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gan N et al (2010) Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27. J Biol Chem 285:35528–35536. https://doi.org/10.1074/jbc.M110.152686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pangeni R, Sahni JK, Ali J, Sharma S, Baboota S (2014) Resveratrol: review on therapeutic potential and recent advances in drug delivery. Expert Opin Drug Deliv 11:1285–1298. https://doi.org/10.1517/17425247.2014.919253

    Article  CAS  PubMed  Google Scholar 

  64. Bastianetto S, Menard C, Quirion R (2015) Neuroprotective action of resveratrol. Biochim Biophys Acta 1852:1195–1201. https://doi.org/10.1016/j.bbadis.2014.09.011

    Article  CAS  PubMed  Google Scholar 

  65. Putics A, Végh EM, Csermely P, Soti C (2008) Resveratrol induces the heat-shock response and protects human cells from severe heat stress. Antioxid Redox Signal 10:65–75. https://doi.org/10.1089/ars.2007.1866

    Article  CAS  PubMed  Google Scholar 

  66. Kim S-Y, Lee H-J, Nam J-W, Seo E-K, Lee Y-S (2015) Coniferyl aldehyde reduces radiation damage through increased protein stability of heat shock transcriptional factor 1 by phosphorylation. Int J Radiat Oncol Biol Phys 91:807–816. https://doi.org/10.1016/j.ijrobp.2014.11.031

    Article  CAS  PubMed  Google Scholar 

  67. Nelson VK et al (2016) Azadiradione ameliorates polyglutamine expansion disease in Drosophila by potentiating DNA binding activity of heat shock factor 1. Oncotarget 7(48):78281–78296

    Article  Google Scholar 

  68. Singh BK et al (2018) Azadiradione restores protein quality control and ameliorates the disease pathogenesis in a mouse model of Huntington’s disease. Mol Neurobiol 55:6337–6346. https://doi.org/10.1007/s12035-017-0853-3

    Article  CAS  PubMed  Google Scholar 

  69. Neef DW, Turski ML, Thiele DJ (2010) Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biol 8:e1000291–e1000291. https://doi.org/10.1371/journal.pbio.1000291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ahn Y-H et al (2010) Electrophilic tuning of the chemoprotective natural product sulforaphane. Proc Natl Acad Sci 107:9590–9595. https://doi.org/10.1073/pnas.1004104107

    Article  PubMed  PubMed Central  Google Scholar 

  71. Zhang Y et al (2014) Sulphoxythiocarbamates modify cysteine residues in HSP90 causing degradation of client proteins and inhibition of cancer cell proliferation. Br J Cancer 110:71–82. https://doi.org/10.1038/bjc.2013.710

    Article  CAS  PubMed  Google Scholar 

  72. Kim SH et al (2001) Activation of heat shock factor 1 by pyrrolidine dithiocarbamate is mediated by its activities as pro-oxidant and thiol modulator. Biochem Biophys Res Commun 281:367–372. https://doi.org/10.1006/bbrc.2001.4376

    Article  CAS  PubMed  Google Scholar 

  73. Zhang Y et al (2011) HSF1-dependent upregulation of Hsp70 by sulfhydryl-reactive inducers of the KEAP1/NRF2/ARE pathway. Chem Biol 18:1355–1361. https://doi.org/10.1016/j.chembiol.2011.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Nagai N, Nakai A, Nagata K (1995) Quercetin suppresses heat shock response by down regulation of HSF1. Biochem Biophys Res Commun 208:1099–1105. https://doi.org/10.1006/bbrc.1995.1447

    Article  CAS  PubMed  Google Scholar 

  75. Li C et al (2016) Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways. Gene 577:275–280. https://doi.org/10.1016/j.gene.2015.12.012

    Article  CAS  PubMed  Google Scholar 

  76. Akagawa H et al (1999) Stresgenin B, an inhibitor of heat-induced heat shock protein gene expression, produced by Streptomyces sp. AS-9. J Antibiot (Tokyo) 52:960–970. https://doi.org/10.7164/antibiotics.52.960

    Article  CAS  Google Scholar 

  77. Westerheide SD, Kawahara TLA, Orton K, Morimoto RI (2006) Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death. J Biol Chem 281:9616–9622. https://doi.org/10.1074/jbc.M512044200

    Article  CAS  PubMed  Google Scholar 

  78. Kim JA, Kim Y, Kwon B-M, Han DC (2013) The natural compound cantharidin induces cancer cell death through inhibition of heat shock protein 70 (HSP70) and Bcl-2-associated athanogene domain 3 (BAG3) expression by blocking heat shock factor 1 (HSF1) binding to promoters. J Biol Chem 288:28713–28726. https://doi.org/10.1074/jbc.M113.488346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim JA et al (2015) Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter. Carcinogenesis 36:696–706. https://doi.org/10.1093/carcin/bgv045

    Article  CAS  PubMed  Google Scholar 

  80. Santagata S et al (2013) Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science 341:1238303–1238303. https://doi.org/10.1126/science.1238303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yoon T, Kang G-Y, Han A-R, Seo E-K, Lee Y-S (2014) 2,4-Bis(4-hydroxybenzyl)phenol inhibits heat shock transcription factor 1 and sensitizes lung cancer cells to conventional anticancer modalities. J Nat Prod 77:1123–1129. https://doi.org/10.1021/np4009333

    Article  CAS  PubMed  Google Scholar 

  82. Nikotina AD et al (2018) Discovery and optimization of cardenolides inhibiting HSF1 activation in human colon HCT-116 cancer cells. Oncotarget 9:27268–27279. https://doi.org/10.18632/oncotarget.25545

    Article  PubMed  PubMed Central  Google Scholar 

  83. Mulholland PJ et al (2001) Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin. Ann Oncol 12:245–248. https://doi.org/10.1023/a:1008372017097

    Article  CAS  PubMed  Google Scholar 

  84. Chugh R et al (2012) A preclinical evaluation of Minnelide as a therapeutic agent against pancreatic cancer. Sci Transl Med 4:156ra139–156ra139. https://doi.org/10.1126/scitranslmed.3004334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zhang D, Zhang B (2016) Selective killing of cancer cells by small molecules targeting heat shock stress response. Biochem Biophys Res Commun 478:1509–1514. https://doi.org/10.1016/j.bbrc.2016.08.108

    Article  CAS  PubMed  Google Scholar 

  86. Yoon YJ et al (2011) KRIBB11 inhibits HSP70 synthesis through inhibition of heat shock factor 1 function by impairing the recruitment of positive transcription elongation factor b to the hsp70 promoter. J Biol Chem 286:1737–1747. https://doi.org/10.1074/jbc.M110.179440

    Article  CAS  PubMed  Google Scholar 

  87. Moore CL et al (2016) Transportable, chemical genetic methodology for the small molecule-mediated inhibition of heat shock factor 1. ACS Chem Biol 11:200–210. https://doi.org/10.1021/acschembio.5b00740

    Article  CAS  PubMed  Google Scholar 

  88. Ohnishi K, Takahashi A, Yokota S, Ohnishi T (2004) Effects of a heat shock protein inhibitor KNK437 on heat sensitivity and heat tolerance in human squamous cell carcinoma cell lines differing in p53 status. Int J Radiat Biol 80:607–614. https://doi.org/10.1080/09553000412331283470

    Article  CAS  PubMed  Google Scholar 

  89. Yokota S, Kitahara M, Nagata K (2000) Benzylidene lactam compound, KNK437, a novel inhibitor of acquisition of thermotolerance and heat shock protein induction in human colon carcinoma cells. Cancer Res 60:2942–2948

    CAS  PubMed  Google Scholar 

  90. Zaarur N, Gabai VL, Porco JA Jr, Calderwood S, Sherman MY (2006) Targeting heat shock response to sensitize cancer cells to proteasome and Hsp90 inhibitors. Cancer Res 66:1783–1791. https://doi.org/10.1158/0008-5472.CAN-05-3692

    Article  CAS  PubMed  Google Scholar 

  91. Menezes K et al (2017) The novel protein HSF1 stress pathway inhibitor Bisamide CCT361814 demonstrates pre-clinical anti-tumor activity in myeloma. Blood 130:3072–3072. https://doi.org/10.1182/blood.V130.Suppl_1.3072.3072

    Article  Google Scholar 

  92. Vilaboa N et al (2017) New inhibitor targeting human transcription factor HSF1: effects on the heat shock response and tumor cell survival. Nucleic Acids Res 45:5797–5817. https://doi.org/10.1093/nar/gkx194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bach M et al (2017) Ugi reaction-derived α-acyl Aminocarboxamides bind to phosphatidylinositol 3-kinase-related kinases, inhibit HSF1-dependent heat shock response, and induce apoptosis in multiple myeloma cells. J Med Chem 60:4147–4160. https://doi.org/10.1021/acs.jmedchem.6b01613

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all the members of Prof. Pal’s laboratory for their support and valuable suggestions to prepare the manuscript. We are grateful to DBT, SERB, and Bose Institute for financial support. ND is an ICMR SRF.

Disclosure of Interests

None of this funding relates to the scientific content of this chapter.

Ethical Approval for Studies Involving Humans

This article does not contain any studies with human participants performed by any of the authors.

Ethical Approval for Studies Involving Animals

This article does not contain any studies with animals performed by any of the authors.

Author information

Authors and Affiliations

  1. Division of Molecular Medicine, Bose Institute, Kolkata, India

    Naibedya Dutta & Mahadeb Pal

  2. Pursuing MBBS, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry, India

    Koustav Pal

Authors
  1. Naibedya Dutta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koustav Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahadeb Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mahadeb Pal .

Editor information

Editors and Affiliations

  1. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Punit Kaur

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dutta, N., Pal, K., Pal, M. (2020). Heat Shock Factor 1 and Its Small Molecule Modulators with Therapeutic Potential. In: Asea, A.A.A., Kaur, P. (eds) Heat Shock Proteins in Inflammatory Diseases. Heat Shock Proteins, vol 22. Springer, Cham. https://doi.org/10.1007/7515_2020_15

Download citation

Publish with us

Policies and ethics

Search

Navigation