{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:55:42Z","timestamp":1778511342198,"version":"3.51.4"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud (CUCS)","award":["271723"],"award-info":[{"award-number":["271723"]}]},{"name":"Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud (CUCS)","award":["1.1.2"],"award-info":[{"award-number":["1.1.2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Hodgkin lymphoma (HL) is a common neoplasm in adolescents and young adults, primarily treated with doxorubicin (DOX) and bleomycin (BLM), which may cause severe adverse effects. The cure rate decreases to 75% in advanced-stage disease, highlighting the need for improved treatment strategies. Pentoxifylline (PTX), an NF-\u03baB pathway inhibitor, enhances chemotherapy-induced apoptosis in cancer cells, making it a promising candidate for HL therapy. This study assessed the effects of PTX, DOX, and BLM on apoptosis, proliferation, and senescence in Hs-445 HL cells. Cell viability and clonogenicity were measured by spectrophotometry and spectrofluorimetry, while apoptosis, caspase activity, cell cycle, mitochondrial membrane potential (\u0394\u03a8m), proliferation, and senescence were analyzed via flow cytometry. Gene expression was assessed by qPCR. PTX significantly induced apoptosis, especially when combined with BLM or BLM+DOX (triple therapy), and modulated gene expression by upregulating proapoptotic and downregulating antiapoptotic markers. PTX increased caspase-3, -8, and -9 activity and disrupted the \u0394\u03a8m, particularly with BLM or triple therapy. Furthermore, PTX abolished DOX-induced G2 cell cycle arrest, reduced proliferation, and clonogenicity, and reversed DOX- and BLM-induced senescence. In conclusion, PTX induces apoptosis in HL cells, enhances DOX and BLM cytotoxicity synergistically, and reverses senescence, suggesting its potential as an adjunct therapy for HL.<\/jats:p>","DOI":"10.3390\/cimb47080593","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T09:53:02Z","timestamp":1753696382000},"page":"593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pentoxifylline Enhances the Effects of Doxorubicin and Bleomycin on Apoptosis, Caspase Activity, and Cell Cycle While Reducing Proliferation and Senescence in Hodgkin\u2019s Disease Cell Line"],"prefix":"10.3390","volume":"47","author":[{"given":"Jes\u00fas A.","family":"Guti\u00e9rrez-Ortiz","sequence":"first","affiliation":[{"name":"Doctoral Program in Biomedical Sciences, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UDG), Guadalajara 44340, JA, Mexico"},{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Guadalajara 44340, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Gonzalez-Ramella","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda Pedi\u00e1trica, Hospital Civil de Guadalajara \u201cDr. Juan I. Menchaca\u201d, Guadalajara 44340, JA, Mexico"},{"name":"Departamento de Reproducci\u00f3n Humana, Crecimiento y Desarrollo Infantil, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UDG), Guadalajara 44340, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-2203","authenticated-orcid":false,"given":"Fabiola","family":"Solorzano-Ibarra","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Enfermedades Cr\u00f3nico Degenerativas, Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UDG), Guadalajara 44340, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Bravo-Cuellar","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Guadalajara 44340, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina","family":"Hern\u00e1ndez-Flores","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Guadalajara 44340, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 A.","family":"Padilla-Ortega","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda, Hospital Civil de Guadalajara \u201cFray Antonio Alcalde\u201d, Guadalajara 44280, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Pelayo-Rubio","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda, Hospital Civil de Guadalajara \u201cFray Antonio Alcalde\u201d, Guadalajara 44280, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge R","family":"Vazquez-Urrutia","sequence":"additional","affiliation":[{"name":"Department of Medicine, Penn State Hershey Medical Center, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-7052","authenticated-orcid":false,"given":"Pablo C.","family":"Ortiz-Lazareno","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Guadalajara 44340, JA, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41572-020-0189-6","article-title":"Hodgkin lymphoma","volume":"6","author":"Connors","year":"2020","journal-title":"Nat. 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