Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia

González-Ramella, Óscar; Ortiz‐Lazareno, Pablo César; Jiménez-López, X.; Gallegos-Castorena, Sergio; Hernández‐Flores, Georgina; Medina-Barajas, Fabiola; Meza-Arroyo, Jesus; Jave‐Suárez, Luis Felipe; Lerma-Díaz, José Manuel; Sánchez-Zubieta, Fernando; Bravo-Cuéllar, Alejandro

doi:10.1007/s12094-015-1376-x

Cited by 11 publications

(6 citation statements)

References 27 publications

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“…Even though PTX is experimentally used to sensitize tumor cells to chemotherapy and can exhibit similar or, in some cases, better efficacy against tumor cell survival, it is not classified as an antitumor drug. In our study, we generated a considerable amount of in vitro evidence of the antitumoral role of PTX, similar to other studies performed in lymphoblastic-leukemia and cervical cancer cells (20,23,24). The importance of this lies in the necessity to find chemotherapeutic agents with fewer adverse effects and robust antitumoral activity.…”

Section: Discussionmentioning

confidence: 53%

“…With more than 30 years of clinical use and fewer adverse effects, PTX (41,42) can provide protection against the adverse symptoms from chemotherapy (43,44). In addition, PTX is not as expensive as other antitumor drugs, and it displays excellent tolerance even in children with cancer (20,21). Due to these characteristics, PTX may represent a new alternative for the treatment of retinoblastoma.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that PTX in combination with antitumoral drugs such as adriamycin, cisplatin, MG132, and perillyl alcohol significantly increases the levels of apoptosis in vivo and in vitro studies, on L5178Y (mouse lymphoma), U937 (human leukemia), and HeLa and SiHa (human cervical cancer cells) (7,(17)(18)(19). Finally, in the clinical setting, it has been demonstrated that PTX can induce cancer remission by increasing apoptosis in children with acute lymphoblastic leukemia during the steroid-window phase (20,21). Similar effects of PTX in other types of cancers have confirmed the potency of this drug (16,(22)(23)(24)(25).…”

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confidence: 98%

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Pentoxifylline Enhances the Apoptotic Effect of Carboplatin in Y79 Retinoblastoma Cells

Cruz-Gálvez

Ortiz‐Lazareno

Pedraza-Brindis

et al. 2019

In Vivo

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Background/Aim: Retinoblastoma (RB) is the most common primary intraocular malignancy. Carboplatin (CPt) is a DNA damage-inducing agent that is widely used for the treatment of RB. Unfortunately, this drug also activates the transcription factor nuclear factor-kappa B (NF-ĸB), leading to promotion of tumor survival. Pentoxifylline (PTX) is a drug that inhibits the phosphorylation of I kappa B-alpha (IĸBα) in serines 32 and 36, and this disrupts NF-ĸB activity that promotes tumor survival. The goal of this study was to evaluate the effect of the PTX on the antitumor activity of CPt. Materials and Methods: Y79 RB cells were treated with CPt, PTX, or both. Cell viability, apoptosis, loss of mitochondrial membrane potential, the activity of caspase-9, -8, and -3, cytochrome c release, cell-cycle progression, p53, and phosphorylation of IĸBα, and pro-and anti-apoptotic genes were evaluated. Results: Both drugs significantly affected the viability of the Y79 RB cells in a time-and dose-dependent manner. The PTX+CPt combination exhibited the highest rate of apoptosis, a decrease in cell viability and significant caspase activation, as well as loss of mitochondrial membrane potential, release of cytochrome c, and increased p53 protein levels. Cells treated with PTX alone displayed decreased I kappa B-alpha phosphorylation, compared to the CPt treated group. In addition, the PTX+CPt combination treatment induced up-regulation of the proapoptotic genes Bax, Bad, Bak, compared to the CPt and PTX individual treated groups. Conclusion: PTX induces apoptosis per se and increases the CPt-induced apoptosis, augmenting its antitumor effectiveness.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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Pentoxifylline Enhances the Apoptotic Effect of Carboplatin in Y79 Retinoblastoma Cells

Cruz-Gálvez

Ortiz‐Lazareno

Pedraza-Brindis

et al. 2019

In Vivo

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“…On its part, PTX is a methylxanthine possessing anti-inflammatory effects that inhibit the NF-κB factor. Antitumor effects have been found per se, and they potentialized chemotherapy and radiotherapy [19,21] and has been reported in leukemic children with encouraging results and minimal adverse effects, such as abdominal pain, nausea, vomiting, and diarrhea, the latter presenting in 3% of patients [22,35]. Thus, it was decided to use PTX as a treatment alternative.…”

Section: Discussionmentioning

confidence: 99%

Management of Hepatocarcinoma with Celecoxib and Pentoxifylline: Report of Three Cases

Mjl¹,

Rf²,

Rv³

et al. 2018

J Clin Exp Pharmacol

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Introduction: Hepatocarcinoma constitutes one of the first five most frequent malignant neoplasms and the third in mortality, being responsible for nearly one million deaths yearly worldwide. In the majority of cases, i.e., 80%, they are diagnosed in advanced stages, with a very poor prognosis, with a survival rate of 8% at three years. Patients submitted to surgery present a recurrence of greater than 70% at five years. In Latin America, infection due to hepatitis C virus constitutes the main cause of hepatocarcinoma, and in Mexico, liver and bile-duct tumors represent the third cause of death by cancer, given the poor prognosis and despite the existing therapeutic schemas. Objective: This report concerns the use of Celecoxib in combination with Pentoxifylline in 3 patients with an advanced stage of hepatocarcinoma disease. Methods: The patients were diagnosed by means of biochemical, serologic, molecular, and imaging studies, in whom management was initiated and continued persistently with Pentoxifylline (400 mg/12 h, per os) plus Celecoxib (100 mg/12 h, per os) and vitamin supplements, clinical and laboratory studies were repeated at the time of cutting. Results: It is noteworthy that three patients present survival of longer than three years with reduction or slight modification of lesion size, as well as improvement in clinical, laboratory, and imaging stage. Conclusion: Although these results are encouraging; controlled studies will be conducted to confirm the efficacy of treatment showed here.

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“…PTX is a dimethyl xanthine proven to significantly increase apoptosis in the leukemic cells of pediatric patients with Acute lymphoblastic leukemia (ALL) during treatment with Prednisone [ 11 ] and to improve the prognosis of patients with hepatocarcinoma [ 12 ]. On its addition, PTX demonstrates an outstanding anti-inflammatory and anti-fibrotic performance [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline Inhibits TNF-α/TGF-β1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and SERPINE1 Expression in CaSki Cells

Palafox-Mariscal,

Ortiz-Lazareno,

Jave-Suárez

et al. 2023

IJMS

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Cervical cancer (CC) is one of the most common and deadly types of female cancer worldwide. Late diagnosis in CC increases the risk of tumor cells spreading to distant organs (metastasis). The epithelial-mesenchymal transition (EMT) is a fundamental process of cancer metastasis. Inflammation can lead to tumor progression, EMT induction, and metastasis. The inflammatory microenvironment is a potent inducer of EMT; inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Transforming growth factor-beta (TGF-β1) activate transcriptional factors such as STAT3, Snail, Smad, and the Nuclear Factor kappa light-chain-enhancer of activated beta cells (NF-κΒ), which drive EMT. Anti-inflammatory compounds may be an option in the disruption of EMT. PenToXifylline (PTX) possesses potent anti-inflammatory effects by inhibiting NF-κB activity. In addition, PTX exerts an anti-fibrotic effect by decreasing Smad2/3/4. We hypothesize that PTX could exert anti-EMT effects. CaSki human cervical tumor cells were exposed to TNF-α 10 ng/mL and TGF-β1 alone or in combination for 5 days. Our results revealed that TNF-α and TGF-β1 induced N-cadherin and Vimentin, confirming the induction of EMT. Furthermore, the combination of cytokines synergized the expression of mesenchymal proteins, enhanced IκBα and p65 phosphorylation, and upregulated Serpin family E member 1 (SERPINE1) mRNA. PTX pretreatment prior to the addition of TNF-α and TGF-β1 significantly reduced N-cadherin and Vimentin levels. To our knowledge, this is the first time that this effect of PTX has been reported. Additionally, PTX reduced the phosphorylation of IκB-α and p65 and significantly decreased SERPINE1 expression, cell proliferation, migration, and invasion. In conclusion, PTX may counteract EMT in cervical cancer cells by decreasing the NF-κB and SERPINE1.

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Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia

Abstract: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.

Cited by 11 publications

References 27 publications

Pentoxifylline Enhances the Apoptotic Effect of Carboplatin in Y79 Retinoblastoma Cells

Pentoxifylline Enhances the Apoptotic Effect of Carboplatin in Y79 Retinoblastoma Cells

Management of Hepatocarcinoma with Celecoxib and Pentoxifylline: Report of Three Cases

Pentoxifylline Inhibits TNF-α/TGF-β1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and SERPINE1 Expression in CaSki Cells

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