Amelioration of Doxorubicin Resistance by Pentoxifylline in Human Chronic Myeloid Leukemia Cells In Vitro

Viladkar, Arundhati; Juvekar, Aarti; Chitnis, M.P.; Advani, Suresh H.

doi:10.1089/sct.1991.7.119

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…This P-gp downregulation observed in L1210/VCR cells was assumed to be responsible for the reversal of the adriamycin or VCR resistance in this cell model [9,19] and the elevation of the intracellular concentrations of both cytostatics. The ability of PTX to potentiate adriamycin toxicity was also described in chronic human myeloid leukemia cells and in P388 leukemia cells [21,22]. In the current paper, we demonstrated a decrease in P-gp protein expression after PTX treatment (Figure 1).…”

Section: Resultssupporting

confidence: 79%

Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

Barančı́k

Boháčová

Gibalová

et al. 2011

IJMS

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The drug efflux activity of P-glycoprotein (P-gp, a product of the mdr1 gene, ABCB1 member of ABC transporter family) represents a mechanism by which tumor cells escape death induced by chemotherapeutics. In this study, we investigated the mechanisms involved in the effects of pentoxifylline (PTX) on P-gp-mediated multidrug resistance (MDR) in mouse leukemia L1210/VCR cells. Parental sensitive mouse leukemia cells L1210, and multidrug-resistant cells, L1210/VCR, which are characterized by the overexpression of P-gp, were used as experimental models. The cells were exposed to 100 μmol/L PTX in the presence or absence of 1.2 μmol/L vincristine (VCR). Western blot analysis indicated a downregulation of P-gp protein expression when multidrug-resistant L1210/VCR cells were exposed to PTX. The effects of PTX on the sensitization of L1210/VCR cells to VCR correlate with the stimulation of apoptosis detected by Annexin V/propidium iodide apoptosis necrosis kit and proteolytic activation of both caspase-3 and caspase-9 monitored by Western blot analysis. Higher release of matrix metalloproteinases (MMPs), especially MMP-2, which could be attenuated by PTX, was found in L1210/VCR than in L1210 cells by gelatin zymography in electrophoretic gel. Exposure of resistant cells to PTX increased the content of phosphorylated Akt kinase. In contrast, the presence of VCR eliminated the effects of PTX on Akt kinase phosphorylation. Taken together, we conclude that PTX induces the sensitization of multidrug-resistant cells to VCR via downregulation of P-gp, stimulation of apoptosis and reduction of MMPs released from drug-resistant L1210/VCR cells. These facts bring new insights into the mechanisms of PTX action on cancer cells.

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Section: Resultssupporting

confidence: 79%

Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

Barančı́k

Boháčová

Gibalová

et al. 2011

IJMS

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“…Importantly, ample evidence has revealed that PTX does not interfere with DOX’s cytotoxicity in several cancer cell lines and it can even synergistically enhance the cytotoxicity of DOX, thereby promoting its therapeutic ability. For instance, in human chronic myeloid leukemia cells, PTX synergistically augments DOX cytotoxicity by increasing DOX accumulation in these cancer cells, culminating in the amelioration of DOX’s resistance [ 43 ]. The combination of PTX and DOX has also demonstrated synergistic activity and dampened cellular proliferation in breast cancer cell lines [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Activation of AMPK/mTOR-Driven Autophagy and Suppression of the HMGB1/TLR4 Pathway with Pentoxifylline Attenuates Doxorubicin-Induced Hepatic Injury in Rats

Arab,

Eid,

Alsufyani

et al. 2024

Pharmaceuticals

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Despite being an effective chemotherapeutic agent, the clinical use of doxorubicin (DOX) is limited by several organ toxicities including hepatic injury. Pentoxifylline (PTX) is a methylxanthine derivative with marked anti-inflammatory and anti-apoptotic features. It is unknown, however, whether PTX can mitigate DOX-evoked hepatotoxicity. This study aims to explore the potential hepatoprotective impact of PTX in DOX-induced hepatic injury and the underlying molecular mechanisms. Histopathology, immunohistochemistry, and ELISA were used to examine liver tissues. The current findings revealed that PTX administration to DOX-intoxicated rats mitigated the pathological manifestations of hepatic injury, reduced microscopical damage scores, and improved serum ALT and AST markers, revealing restored hepatic cellular integrity. These favorable effects were attributed to PTX’s ability to mitigate inflammation by reducing hepatic IL-1β and TNF-α levels and suppressing the pro-inflammatory HMGB1/TLR4/NF-κB axis. Moreover, PTX curtailed the hepatic apoptotic abnormalities by suppressing caspase 3 activity and lowering the Bax/Bcl-2 ratio. In tandem, PTX improved the defective autophagy events by lowering hepatic SQSTM-1/p62 accumulation and enhancing the AMPK/mTOR pathway, favoring autophagy and hepatic cell preservation. Together, for the first time, our findings demonstrate the ameliorative effect of PTX against DOX-evoked hepatotoxicity by dampening the hepatic HMGB1/TLR4/NF-κB pro-inflammatory axis and augmenting hepatic AMPK/mTOR-driven autophagy. Thus, PTX could be utilized as an adjunct agent with DOX regimens to mitigate DOX-induced hepatic injury.

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“…Alpha-enolase is a multifunctional glycolytic enzyme and may provide carbohydrates for energy requirements of cognitive function. [58][59][60] It has been reported in the mouse hippocampus (http://www.expasy.org/uniprot/P17182) but is poorly characterized at the protein level. It was well-characterized by 25 matching spots and several sequence conflicts were observed.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Enhancement by SGS742 in OF1 Mice Is Linked to Specific Hippocampal Protein Expression

et al. 2008

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Cognitive enhancement by the GABA (B) antagonist SGS742 has been reported and we decided to search for proteins involved. Hippocampi from OF1 mice were from SGS742- treated animals and three control groups. Proteins were extracted and run on 2DE, and spots were quantified. Significantly different protein spots were identified by two mass spectrometry principles, nano-LC-ESI-MS/MS and by nano-LC-ESI(CID/ETD)-MS/MS. Signaling, chaperone and metabolic enzyme proteins were linked to memory enhancement.

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Amelioration of Doxorubicin Resistance by Pentoxifylline in Human Chronic Myeloid Leukemia Cells In Vitro

Cited by 7 publications

References 15 publications

Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

Activation of AMPK/mTOR-Driven Autophagy and Suppression of the HMGB1/TLR4 Pathway with Pentoxifylline Attenuates Doxorubicin-Induced Hepatic Injury in Rats

Cognitive Enhancement by SGS742 in OF1 Mice Is Linked to Specific Hippocampal Protein Expression

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