ArticleJournal of biomedical science2013
Pentoxifylline and the proteasome inhibitor MG132 induce apoptosis in human leukemia U937 cells through a decrease in the expression of Bcl-2 and Bcl-XL and phosphorylation of p65.
Article in Journal of biomedical science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05490953 (Enhancing Effect on Tumour Apoptosis With the Combined Use of Pentoxifylline Plus Chemotherapeutical Agents in Pediatrics and AYA Patients With Hodgkin´s Lymphoma), which is not on this map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Enhancing Effect on Tumour Apoptosis With the Combined Use of Pentoxifylline Plus Chemotherapeutical Agents in Pediatrics and AYA Patients With Hodgkin´s Lymphoma
Who cites it
12 citing papers in PubMed, 34 citations in OpenAlex.
- Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Trial
- Pentoxifylline Enhances the Effects of Doxorubicin and Bleomycin on Apoptosis, Caspase Activity, and Cell Cycle While Reducing Proliferation and Senescence in Hodgkin's Disease Cell Line.Current issues in molecular biology · 2025Article
- Chemotherapy with a molecular rational basis, pentoxifylline as a promising antitumor drug.Annals of medicine and surgery (2012) · 2025Review
- Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia.Frontiers in oncology · 2024Article
- Retinoblastoma: Review and new insights.Frontiers in oncology · 2022Review
- miR‑383 increases the cisplatin sensitivity of lung adenocarcinoma cells through inhibition of the RBM24‑mediated NF‑κB signaling pathway.International journal of oncology · 2021Article
- Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line.BMC urology · 2021Article
- Pentoxifylline Sensitizes Cisplatin-Resistant Human Cervical Cancer Cells to Cisplatin Treatment: Involvement of Mitochondrial and NF-Kappa B Pathways.Frontiers in oncology · 2020Article
- Article
- ABT-737 Synergizes with Cisplatin Bypassing Aberration of Apoptotic Pathway in Non-small Cell Lung Cancer.Neoplasia (New York, N.Y.) · 2017Article
- c-Rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells.The Journal of biological chemistry · 2014Article
- Pentoxifylline Enhances the Apoptotic Effect of Carboplatin in Y79 Retinoblastoma Cells.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn Oncology, the resistance of the cancerous cells to chemotherapy continues to be the principal limitation. The nuclear factor-kappa B (NF-κB) transcription factor plays an important role in tumor escape and resistance to chemotherapy and this factor regulates several pathways that promote tumor survival including some antiapoptotic proteins such as Bcl-2 and Bcl-XL. In this study, we investigated, in U937 human leukemia cells, the effects of PTX and the MG132 proteasome inhibitor, drugs that can disrupt the NF-κB pathway. For this, we evaluated viability, apoptosis, cell cycle, caspases-3, -8, -9, cytochrome c release, mitochondrial membrane potential loss, p65 phosphorylation, and the modification in the expression of pro- and antiapoptotic genes, and the Bcl-2 and Bcl-XL antiapoptotic proteins.
resultsThe two drugs affect the viability of the leukemia cells in a time-dependent manner. The greatest percentage of apoptosis was obtained with a combination of the drugs; likewise, PTX and MG132 induce G1 phase cell cycle arrest and cleavage of caspases -3,-8, -9 and cytochrome c release and mitochondrial membrane potential loss in U937 human leukemia cells. In these cells, PTX and the MG132 proteasome inhibitor decrease p65 (NF-κB subunit) phosphorylation and the antiapoptotic proteins Bcl-2 and Bcl-XL. We also observed, with a combination of these drugs overexpression of a group of the proapoptotic genes BAX, DIABLO, and FAS while the genes BCL-XL, MCL-1, survivin, IκB, and P65 were downregulated.
conclusionsThe two drugs used induce apoptosis per se, this cytotoxicity was greater with combination of both drugs. These observations are related with the caspases -9, -3 cleavage and G1 phase cell cycle arrest, and a decrease in p65 phosphorylation and Bcl-2 and Bcl-XL proteins. As well as this combination of drugs promotes the upregulation of the proapoptotic genes and downregulation of antiapoptotic genes. These observations strongly confirm antileukemic potential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.