{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:02:57Z","timestamp":1792789377605,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"RSF","doi-asserted-by":"publisher","award":["19-75-20128"],"award-info":[{"award-number":["19-75-20128"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["19-75-20128"],"award-info":[{"award-number":["19-75-20128"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The tumor microenvironment (TME) plays an essential role in tumor progression and in modulating tumor response to anticancer therapy. Cellular senescence leads to a switch in the cell secretome, characterized by the senescence-associated secretory phenotype (SASP), which may regulate tumorigenesis. Senolytic therapy is considered a novel anticancer strategy that eliminates the deleterious effects of senescent cells in the TME. Here, we show that two different types of senolytic drugs, despite efficiently depleting senescent cells, have opposite effects on cancer-associated fibroblasts (CAFs) and their ability to regulate epithelial\u2013mesenchymal transition (EMT). We found that senolytic drugs, navitoclax and the combination of dasatinib\/quercetin, reduced the number of spontaneously senescent and TNF-induced senescent CAFs. Despite the depletion of senescent cells, the combination of dasatinib\/quercetin versus navitoclax increased the secretion of the SASP pro-inflammatory cytokine IL-6. This differential effect correlated with the promotion of enhanced migration and EMT in MC38 colorectal cancer cells. Our results demonstrate that some senolytics may have side effects unrelated to their senolytic activity and may promote tumorigenesis. We argue for more careful and extensive studies of the effects of senolytics on various aspects of tumor progression and tumor resistance to therapy before the senolytic strategy is implemented in the clinic.<\/jats:p>","DOI":"10.3390\/ijms25074031","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T10:42:03Z","timestamp":1712227323000},"page":"4031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2851-3775","authenticated-orcid":false,"given":"Daria A.","family":"Bogdanova","sequence":"first","affiliation":[{"name":"Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, Sirius, Krasndarsky Krai, 354340 Sochi, Russia"},{"name":"Institute of Cytology RAS, 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina D.","family":"Kolosova","sequence":"additional","affiliation":[{"name":"Institute of Cytology RAS, 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4250-2693","authenticated-orcid":false,"given":"Tamara V.","family":"Pukhalskaia","sequence":"additional","affiliation":[{"name":"Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, Sirius, Krasndarsky Krai, 354340 Sochi, Russia"},{"name":"Institute of Cytology RAS, 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-2496","authenticated-orcid":false,"given":"Ksenia A.","family":"Levchuk","sequence":"additional","affiliation":[{"name":"World-Class Research Centre for Personalized Medicine, Almazov National Medical Research Centre, 197341 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4323-7174","authenticated-orcid":false,"given":"Oleg N.","family":"Demidov","sequence":"additional","affiliation":[{"name":"Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, Sirius, Krasndarsky Krai, 354340 Sochi, Russia"},{"name":"Institute of Cytology RAS, 194064 St. Petersburg, Russia"},{"name":"INSERM UMR1231, University of Burgundy, 21078 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-9552","authenticated-orcid":false,"given":"Ekaterina V.","family":"Belotserkovskaya","sequence":"additional","affiliation":[{"name":"Institute of Cytology RAS, 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.tips.2023.01.003","article-title":"Metastatic Colorectal Cancer: Mechanisms and Emerging Therapeutics","volume":"44","author":"Shin","year":"2023","journal-title":"Trends Pharmacol. 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