{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:18:36Z","timestamp":1790716716117,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,13]],"date-time":"2018-03-13T00:00:00Z","timestamp":1520899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Classical Hodgkin lymphoma (cHL) cells overexpress heat-shock protein 90 (HSP90), an important intracellular signaling hub regulating cell survival, which is emerging as a promising therapeutic target. Here, we report the antitumor effect of celastrol, an anti-inflammatory compound and a recognized HSP90 inhibitor, in Hodgkin and Reed\u2013Sternberg cell lines. Two disparate responses were recorded. In KM-H2 cells, celastrol inhibited cell proliferation, induced G0\/G1 arrest, and triggered apoptosis through the activation of caspase-3\/7. Conversely, L428 cells exhibited resistance to the compound. A proteomic screening identified a total of 262 differentially expressed proteins in sensitive KM-H2 cells and revealed that celastrol\u2019s toxicity involved the suppression of the MAPK\/ERK (extracellular signal regulated kinase\/mitogen activated protein kinase) pathway. The apoptotic effects were preceded by a decrease in RAS (proto-oncogene protein Ras), p-ERK1\/2 (phospho-extracellular signal-regulated Kinase-1\/2), and c-Fos (proto-oncogene protein c-Fos) protein levels, as validated by immunoblot analysis. The L428 resistant cells exhibited a marked induction of HSP27 mRNA and protein after celastrol treatment. Our results provide the first evidence that celastrol has antitumor effects in cHL cells through the suppression of the MAPK\/ERK pathway. Resistance to celastrol has rarely been described, and our results suggest that in cHL it may be mediated by the upregulation of HSP27. The antitumor properties of celastrol against cHL and whether the disparate responses observed in vitro have clinical correlates deserve further research.<\/jats:p>","DOI":"10.3390\/ijms19030836","type":"journal-article","created":{"date-parts":[[2018,3,13]],"date-time":"2018-03-13T13:37:21Z","timestamp":1520948241000},"page":"836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeting Hodgkin and Reed\u2013Sternberg Cells with an Inhibitor of Heat-Shock Protein 90: Molecular Pathways of Response and Potential Mechanisms of Resistance"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-9243","authenticated-orcid":false,"given":"Priscilla","family":"Segges","sequence":"first","affiliation":[{"name":"Oncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephany","family":"Corr\u00eaa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio C\u00e9lula-Tronco, CEMO, Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Du Rocher","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio C\u00e9lula-Tronco, CEMO, Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"},{"name":"Laborat\u00f3rio de Pesquisa sobre o Timo, FIOCRUZ, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-337X","authenticated-orcid":false,"given":"Gabriela","family":"Vera-Lozada","sequence":"additional","affiliation":[{"name":"Oncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Krsticevic","sequence":"additional","affiliation":[{"name":"Oncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"},{"name":"CIFASIS\u2014Centro Internacional Franco Argentino de Ciencias de la Informaci\u00f3n y de Sistemas, Rosario 4237248, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Arce","sequence":"additional","affiliation":[{"name":"CIFASIS\u2014Centro Internacional Franco Argentino de Ciencias de la Informaci\u00f3n y de Sistemas, Rosario 4237248, Argentina"},{"name":"IICAR-CONICET Instituto de Ciencias Agrarias de Rosario, Rosario 4237248, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinthya","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Translacional, Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Abdelhay","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio C\u00e9lula-Tronco, CEMO, Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3782-3580","authenticated-orcid":false,"given":"Rocio","family":"Hassan","sequence":"additional","affiliation":[{"name":"Oncovirology Laboratory, Bone Marrow Transplantation Center (CEMO), Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20230-130, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrc2542","article-title":"The biology of Hodgkin\u2019s lymphoma","volume":"9","author":"Kuppers","year":"2009","journal-title":"Nat. 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