{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:20:46Z","timestamp":1782915646496,"version":"3.54.5"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Medical Research Council-Self-Initiated Grants (SAMRC-SIR)","award":["2019-466-3"],"award-info":[{"award-number":["2019-466-3"]}]},{"name":"Sapienza University of Rome","award":["2019-466-3"],"award-info":[{"award-number":["2019-466-3"]}]},{"name":"International PAs Foundation ONLUS-ETS","award":["2019-466-3"],"award-info":[{"award-number":["2019-466-3"]}]},{"name":"Ministry of Education and Research (BMBF)","award":["2019-466-3"],"award-info":[{"award-number":["2019-466-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Environmental stimuli can distress the internal reaction of cells and their normal function. To react promptly to sudden environmental changes, a cascade of heat shock proteins (Hsps) functions to protect and act as housekeepers inside the cells. In parallel to the heat shock response, the metabolic polyamine (PA) status changes. Here, we discuss possible ways of putative interactions between Hsps and polyamines in a wide lineage of eukaryotic model organisms with a particular focus on parasitic protozoa such as Plasmodium falciparum (P. falciparum). The supposed interaction between polyamines and Hsps may protect the parasite from the sudden change in temperature during transmission from the female Anopheles mosquito to a human host. Recent experiments performed with the spermidine mimetic inhibitor 15-deoxyspergualine in Plasmodium in vitro cultures show that the drug binds to the C-terminal EEVD motif of Hsp70. This leads to inhibition of protein biosynthesis caused by prevention of eIF5A2 phosphorylation and eukaryotic initiation factor 5A (eIF5A) modification. These observations provide further evidence that PAs are involved in the regulation of protein biosynthesis of Hsps to achieve a protective effect for the parasite during transmission.<\/jats:p>","DOI":"10.3390\/molecules28041686","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T01:35:29Z","timestamp":1675992929000},"page":"1686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An Undefined Interaction between Polyamines and Heat Shock Proteins Leads to Cellular Protection in Plasmodium falciparum and Proliferating Cells in Various Organisms"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-4619","authenticated-orcid":false,"given":"Xolani H.","family":"Makhoba","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Biotechnology, School of Molecular and Life Science, University of Limpopo, Turfloop Campus, Sovenga 0727, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5399-975X","authenticated-orcid":false,"given":"Rino","family":"Ragno","sequence":"additional","affiliation":[{"name":"Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University, P. le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7873-3958","authenticated-orcid":false,"given":"Annette","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Medical Research Centre, University of Duisburg-Essen, Hufeland Strasse 55, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2508-8868","authenticated-orcid":false,"given":"Enzo","family":"Agostinelli","sequence":"additional","affiliation":[{"name":"Department of Sensory Organs, Sapienza University of Rome, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy"},{"name":"International Polyamines Foundation \u2018ETS-ONLUS\u2019, Via del Forte Tiburtino 98, 00159 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.biocel.2009.07.009","article-title":"Modulation of cellular function by polyamines","volume":"42","author":"Igarashi","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14904","DOI":"10.1074\/jbc.R116.731661","article-title":"Functions of Polyamines in Mammals","volume":"291","author":"Pegg","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/BF02172188","article-title":"A new puffing pattern induced by temperature shock and DNP in Drosophila","volume":"18","author":"Ritossa","year":"1962","journal-title":"Experientia"},{"key":"ref_4","first-page":"38","article-title":"Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue","volume":"269","author":"Matz","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s004240050905","article-title":"TGF-beta1 mediates 70-kDa heat shock protein induction due to ultraviolet irradiation in human skin fibroblasts","volume":"438","author":"Cao","year":"1999","journal-title":"Pfl\u00fcgers Archiv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1177\/002215549804601109","article-title":"Expression of heat shock proteins in mouse skin during wound healing","volume":"46","author":"Laplante","year":"1998","journal-title":"J. Histochem. Cytochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/10520295.2017.1421322","article-title":"Age-related lung tissue remodeling due to the local distribution of MMP-2, TIMP-2, TGF-\u03b2 and Hsp70","volume":"93","author":"Vitenberga","year":"2018","journal-title":"Biotech. Histochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-3-030-40204-4_3","article-title":"Regulation of Hsf1 and the Heat Shock Response","volume":"1243","author":"Pincus","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7858","DOI":"10.1038\/s41598-020-64746-2","article-title":"Genome-wide Identification and Characterization of Heat Shock Protein Family Reveals Role in Development and Stress Conditions in Triticum aestivum L.","volume":"12","author":"Kumar","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.3389\/fpls.2018.01945","article-title":"Polyamine Function in Plants: Metabolism, Regulation on Development, and Roles in Abiotic Stress Responses","volume":"9","author":"Chen","year":"2019","journal-title":"Front. Plant Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fenvs.2015.00021","article-title":"Polyamines as redox homeostasis regulators during salt stress in plants","volume":"3","author":"Saha","year":"2015","journal-title":"Front. Environ. Sci."},{"key":"ref_12","first-page":"72","article-title":"Accumulation of free polyamines enhances the antioxidant response in fruits of grafted tomato plants under water stress","volume":"190","author":"Romero","year":"2015","journal-title":"J. Plant Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.plaphy.2018.05.034","article-title":"Modulation of polyamine biosynthesis in Arabidopsis thaliana by a drought mitigating Pseudomonas putida strain","volume":"129","author":"Sen","year":"2018","journal-title":"Plant Physiol. Biochem."},{"key":"ref_14","first-page":"173","article-title":"Global metabolic profiling of Arabidopsis polyamine oxidase 4 (AtPAO4) loss-of-function mutants exhibiting delayed dark-induced senescence","volume":"7","author":"Sequeramutiozabal","year":"2016","journal-title":"Front. Plant Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0981-9428(01)01347-X","article-title":"Are polyamines involved in the synthesis of heat-shock proteins in cell suspension cultures of tobacco and alfalfa in response to hightemperature stress?","volume":"40","author":"Lechner","year":"2002","journal-title":"Plant Physiol. Biochem."},{"key":"ref_16","first-page":"850","article-title":"Polyamines as Modulators of Gene Expression under Oxidative Stress in Escherichia coli","volume":"68","author":"Tkachenko","year":"2003","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.3389\/fpls.2019.01331","article-title":"Increasing Polyamine Contents Enhances the Stress Tolerance via Reinforcement of Antioxidative Properties","volume":"10","author":"Seo","year":"2019","journal-title":"Front. Plant Sci."},{"key":"ref_18","first-page":"57","article-title":"The apicoplast: A review of the derived plastid of apicomplexan parasite","volume":"7","author":"Waller","year":"2005","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_19","unstructured":"(2021). World Malaria Report 2021, World Health Organization."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1074\/jbc.M807085200","article-title":"Co-inhibition of Plasmodium falciparum S-Adenosylmethionine Decarboxylase\/Ornithine Decarboxylase Reveals Perturbation-specific Compensatory Mechanisms by Transcriptome, Proteome, and Metabolome Analyses","volume":"284","author":"Olszewski","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.pt.2009.10.006","article-title":"Vitamin B metabolism in Plasmodium falciparum as a source of drug targets","volume":"26","author":"Hyde","year":"2010","journal-title":"Trends Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1128\/EC.00160-14","article-title":"Isoprenoid biosynthesis in Plasmodium falciparum","volume":"13","author":"Guggisberg","year":"2014","journal-title":"Eucaryot. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12936-019-2651-z","article-title":"Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase: Characterization of the Plasmodium vivax enzyme and inhibitor studies","volume":"25","author":"Haeussler","year":"2019","journal-title":"Malaria J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.2174\/1381612823666170601101644","article-title":"Parasite Polyamines as Pharmaceutical Targets","volume":"23","author":"Roberts","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-3-030-78397-6_10","article-title":"Heat Shock Proteins of Malaria: Highlights and Future Prospects","volume":"1340","author":"Shonhai","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_26","first-page":"eaar2606","article-title":"Oil for the cancer engine: The cross-talk between oncogenic signaling and polyamine metabolism","volume":"24","author":"Carracedo","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0065-2571(85)90072-X","article-title":"Ornithine as a target of chemotherapy","volume":"24","author":"Heby","year":"1985","journal-title":"Adv. Enzym. Regul."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113846","DOI":"10.1016\/j.ejmech.2021.113846","article-title":"The heat shock response and small molecule regulators","volume":"15","author":"Kurop","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0014-5793(99)00873-X","article-title":"Influence of polyamines on DNA binding of heat shock and activator protein 1 transcription factors induced by heat shock","volume":"16","author":"Desiderio","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/hep.510240125","article-title":"Effects of polyamine imbalance on the induction of stress genes in hepatocarcinoma cells exposed to heat shock","volume":"4","author":"Desiderio","year":"1996","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.1074\/jbc.271.10.5656","article-title":"DNA aggregation induced by polyamines and cobalthexamine","volume":"271","author":"Pelta","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8967","DOI":"10.1021\/acsomega.9b00784","article-title":"Effects of Polyamine Binding on the Stability of DNA i-Motif Structures","volume":"4","author":"Michael","year":"2019","journal-title":"ACS Omega"},{"key":"ref_33","first-page":"1172","article-title":"Biogenic polyamines spermine and spermidine activate RNA polymerase and inhibit RNA helicase of hepatitis C virus","volume":"77","author":"Korovina","year":"2012","journal-title":"Biochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.envint.2019.04.025","article-title":"Global heat stress on health, wildfires, and agricultural crops under different levels of climate warming","volume":"128","author":"Sun","year":"2019","journal-title":"Environ. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.plaphy.2018.08.017","article-title":"Overexpression of alfalfa Orange gene in tobacco enhances carotenoid accumulation and tolerance to multiple abiotic stresses","volume":"130","author":"Wang","year":"2018","journal-title":"Plant Physiol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/jipb.12128","article-title":"Improvement of plant abiotic stress tolerance through modulation of the polyamine pathway","volume":"56","author":"Shi","year":"2014","journal-title":"J. Integr. Plant Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Toumi, I., Pagoulatou, M.G., Margaritopoulou, T., Milioni, D., and Roubelakis-Angelakis, K.A. (2019). Genetically modified heat shock protein90s and polyamine oxidases in Arabidopsis reveal their Interaction under heat stress affecting polyamine acetylation, oxydation and homeostasis of reactive oxygen species. Plants, 3.","DOI":"10.3390\/plants8090323"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jplph.2017.08.006","article-title":"Underexpression of apoplastic polyamine oxidase improves thermotolerance in Nicotiana tabacum","volume":"218","author":"Mellidou","year":"2017","journal-title":"J. Plant Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e110923","DOI":"10.1016\/j.plantsci.2021.110923","article-title":"Unfinished story of polyamines: Role of conjugation, transport and light-related regulation in the polyamine metabolism in plants","volume":"308","author":"Szalai","year":"2021","journal-title":"Plant Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Upadhyay, R.K., Fatima, T., Handa, A.K., and Mattoo, A.K. (2020). Polyamines and Their Biosynthesis\/Catabolism Genes Are Differentially Modulated in Response to Heat Versus Cold Stress in Tomato Leaves (Solanum lycopersicum L.). Cells, 9.","DOI":"10.3390\/cells9081749"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s11033-014-3826-x","article-title":"Heat shock factors in carrot: Genome-wide identification, classification, and expression profiles response to abiotic stress","volume":"42","author":"Huang","year":"2015","journal-title":"Mol Biol. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1152\/ajpgi.00054.2011","article-title":"Polyamines mediate glutamine-dependent induction of the intestinal epithelial heat shock response","volume":"301","author":"Iwashita","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Alc\u00e1zar, R., Bueno, M., and Tiburcio, A.F. (2020). Polyamines: Small Amines with Large Effects on Plant Abiotic Stress Tolerance. Cells, 9.","DOI":"10.3390\/cells9112373"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.plaphy.2022.09.025","article-title":"Over-expression of spermidine synthase 2 (SlSPDS2) in tomato plants improves saline-alkali stress tolerance by increasing endogenous polyamines content to regulate antioxidant enzyme system and ionic homeostasis","volume":"192","author":"Wang","year":"2020","journal-title":"Plant Physiol. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/plb.13139","article-title":"Metabolic regulation of polyamines and \u03b3-aminobutyric acid in relation to spermidine-induced heat tolerance in white clover","volume":"22","author":"Luo","year":"2020","journal-title":"Plant Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12192-011-0299-x","article-title":"Characterisation of the Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop)","volume":"17","author":"Gitau","year":"2012","journal-title":"Cell Stress Chaperones"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zininga, T., Ramatsui, L., Makhado, P.B., Makumire, S., Achilinou, I., Hoppe, H., Dirr, H., and Shonhai, A. (2017). (-)-Epigallocatechin-3-Gallate Inhibits the Chaperone Activity of Plasmodium falciparum Hsp70 Chaperones and Abrogates Their Association with Functional Partners. Molecules, 22.","DOI":"10.3390\/molecules22122139"},{"key":"ref_48","first-page":"34","article-title":"Plasmodial HSP70s are functionally adapted to the malaria parasite life cycle","volume":"26","author":"Przyborski","year":"2015","journal-title":"Front. Mol. Biosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1186\/1475-2875-13-118","article-title":"Identification of heat shock factor binding protein in Plasmodium falciparum","volume":"13","author":"Sayeed","year":"2014","journal-title":"Malaria J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1042\/BJ20060879","article-title":"15-deoxyspergualin inhibits eukaryotic protein synthesis through eIF2alpha phosphorylation","volume":"401","author":"Ramya","year":"2007","journal-title":"Biochem. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6388","DOI":"10.1074\/jbc.M610251200","article-title":"15-Deoxyspergualin primarily targets the trafficking of Apicoplast proteins in Plasmodium falciparum","volume":"282","author":"Ramya","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bbrc.2006.07.082","article-title":"15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function","volume":"348","author":"Ramya","year":"2006","journal-title":"Biochem. Biophys. Res. Comm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1042\/bj3630761","article-title":"Inhibition of cell growth through inactivation of eukaryotic translation initiation factor 5A (eIF5A) by deoxyspergualin","volume":"363","author":"Nishimura","year":"2002","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8097","DOI":"10.1074\/jbc.275.11.8097","article-title":"In the human malaria parasite Plasmodium falciparum, polyamines are synthesized by a bifunctional ornithine decarboxylase, S-adenosylmethionine decarboxylase","volume":"275","author":"Wrenger","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1515\/BC.2008.014","article-title":"Transcriptional responses of Plasmodium falciparum to alpha-difluoromethylornithine-induced polyamine depletion","volume":"389","author":"Clark","year":"2008","journal-title":"Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Becker, J.V., Mtwisha, L., Crampton, B.G., Stoychev, S., van Brummelen, A.C., Reeksting, S., Louw, A.I., Birkholtz, L.M., and Mancama, D.T. (2010). Plasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein and metabolite level. BMC Genom., 11.","DOI":"10.1186\/1471-2164-11-235"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.str.2015.03.002","article-title":"Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination","volume":"23","author":"Han","year":"2015","journal-title":"Structure"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5881","DOI":"10.1111\/j.1742-4658.2009.07272.x","article-title":"Completing the hypusine pathway in Plasmodium","volume":"276","author":"Frommholz","year":"2009","journal-title":"FEBS J."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Yun, C.W., Kim, H.J., Lim, J.H., and Lee, S.H. (2019). Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy. Cells, 9.","DOI":"10.3390\/cells9010060"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Choi, S.K., Kam, H., Kim, K.Y., Park, S.I., and Lee, Y.S. (2019). Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment?. Cancers, 11.","DOI":"10.20944\/preprints201907.0081.v1"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1158\/1078-0432.CCR-17-2619","article-title":"HSP27-Mediated Extracellular and Intracellular Signaling Pathways synergistically Ccnfer Chemoresistance in Squamous Cell Carcinoma of Tongue","volume":"24","author":"Zheng","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_62","first-page":"4258","article-title":"Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer","volume":"61","author":"Shridhar","year":"2001","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.canlet.2018.03.004","article-title":"EGFR-TKI-induced HSP70 degradation and BER suppression facilitate the occurrence of the EGFR T790M resistant mutation in lung cancer cells","volume":"424","author":"Cao","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.2147\/IJGM.S318271","article-title":"Single-Cell Sequencing to Identify Six Heat Shock Protein (HSP) Genes-Mediated Progression Subtypes of Clear Cell Renal Cell Carcinoma","volume":"14","author":"Li","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41568-018-0050-3","article-title":"Polyamine metabolism and cancer: Treatments, challenges and opportunities","volume":"18","author":"Casero","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41568-022-00473-2","article-title":"Polyamines in cancer: Integrating organismal metabolism and antitumour immunity","volume":"22","author":"Holbert","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_67","first-page":"481","article-title":"Growth arrest- and polyamine-dependent expression of spermidine\/spermine N1-acetyltransferase in human tumor cells","volume":"7","author":"Ignatenko","year":"1996","journal-title":"Cell Growth Differ."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/mt.2012.94","article-title":"Modulation of eIF5A expression using SNS01 nanoparticles inhibits NF-\u03baB activity and tumor growth in murine models of multiple myeloma","volume":"20","author":"Taylor","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1158\/0008-5472.CAN-13-0474","article-title":"Blocking eIF5A modification in cervical cancer cells alters the expression of cancer-related genes and suppresses cell proliferation","volume":"74","author":"Hoque","year":"2014","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/nature11126","article-title":"A tumour suppressor network relying on the polyamine-hypusine axis","volume":"487","author":"Scuoppo","year":"2012","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/bs.podrm.2018.11.003","article-title":"Sorafenib","volume":"44","author":"Abdelgalil","year":"2019","journal-title":"Profiles Drug Subst. Excip. Relat. Methodol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhang, J., Li, H., Liu, Y., Zhao, K., Wei, S., Sugarman, E.T., Liu, L., and Zhang, G. (2022). Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance. Cells, 6.","DOI":"10.3390\/cells11182778"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3892\/mmr.2015.4600","article-title":"Suppression of HSP27 increases the antitumor effects of quercetin in human leukemia U937 cells","volume":"13","author":"Chen","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.chembiol.2017.04.008","article-title":"Mitochondrial Chaperonin HSP60 Is the Apoptosis-Related Target for Myrtucommulone","volume":"24","author":"Wiechmann","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"28713","DOI":"10.1074\/jbc.M113.488346","article-title":"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","volume":"288","author":"Kim","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"41294","DOI":"10.18632\/oncotarget.17180","article-title":"Efficacy of an HSP90 inhibitor, ganetespib, in preclinical thyroid cancer models","volume":"8","author":"Lin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00726-020-02843-2","article-title":"Inhibition of EIF-5A prevents apoptosis in human cardiomyocytes after malaria infection","volume":"52","author":"Kaiser","year":"2020","journal-title":"Amino Acids"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13737","DOI":"10.1038\/srep13737","article-title":"Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis","volume":"8","author":"Seko","year":"2015","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1686\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:29:37Z","timestamp":1760120977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,10]]},"references-count":78,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041686"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041686","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,10]]}}}