Pentoxifylline as a modulator of anticancer drug doxorubicin. Part II: Reduction of doxorubicin DNA binding and alleviation of its biological effects

Gołuński, Grzegorz; Borowik, Agnieszka; Derewońko, Natalia; Kawiak, Anna; Rychłowski, Michał; Woziwodzka, Anna; Piosik, Jacek

doi:10.1016/j.biochi.2016.02.003

Cited by 23 publications

(21 citation statements)

References 39 publications

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“…). In addition, potential protective effects of PTX towards DOX‐induced side‐effects have been reported, based on the capacity of PTX to sequester aromatic compounds (DOX) in staking complexes …”

Section: Discussionmentioning

confidence: 99%

“…a). High tumor cell density (tumor hyperplasia) may also create an interstitial barrier for penetration of drug molecules . Cell killing by GEM itself may therefore have augmented the reduction in solid stress, synergistically improving drug (GEM) delivery.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, potential protective effects of PTX towards DOX-induced side-effects have been reported, based on the capacity of PTX to sequester aromatic compounds (DOX) in staking complexes. (34,35) In the present study, we tested the hypothesis that the synergistic interaction between PTX and GEM (Fig. 1a) may be a result of improved drug distribution in tumors (pharmacokinetic modulation).…”

Section: Discussionmentioning

confidence: 99%

“…High tumor cell density (tumor hyperplasia) may also create an interstitial barrier for penetration of drug molecules. (35) Cell killing by GEM itself may therefore have augmented the reduction in solid stress, synergistically improving drug (GEM) delivery. Other antifibrotic agents, such as halofuginone, losartan, and the hedgehog inhibitor IPI-926, also demonstrated that their synergistic interactions with various chemotherapeutic agents involved modulation of drug distribution.…”

Section: Discussionmentioning

confidence: 99%

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Antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts

et al. 2017

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We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM. PTX given for 2 weeks prior to giving DOX improved drug distribution by 1.8‐ to 2.2‐fold with no changes in vessel density, suggesting that improvement in drug delivery was not related to the vascular mechanism. Instead, collagen I content in tumor stroma was significantly reduced, as was the expression of alpha‐smooth muscle actin of cancer‐associated fibroblasts and connective tissue growth factor (CTGF) by PTX pretreatment. Overall, our data demonstrated that increased efficacy of GEM by PTX was associated with improved drug delivery to tumor tissue, which may be attributed to decreased expression of CTGF and subsequent reduction in the stromal collagen matrix in the pancreatic ductal adenocarcinoma tumor. These results support the usefulness of PTX in combination with chemotherapy for targeting drug delivery barriers associated with the stromal matrix, which should be further evaluated for clinical development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts

et al. 2017

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“…DOX also interacts with the cell membrane and mitochondria, resulting in generation of reactive oxygen species leading to direct membrane damage and oxidative stress, responsible for the major DOX side effect, cardiomyopathy. [35,[40][41][42] DNA remains the main target of cancer therapeutics, whereby induction of DNA damage initiates a cascade of events that determines cellular apoptosis. DNA damage level and repair, by expression of anti-apoptotic proteins such as bcl-2 and resistance to apoptosis, are the main processes involved in carcinogenesis and in the response of cancer cells to cancer chemotherapy.…”

Section: B Drug Screeningmentioning

confidence: 99%

Advancing Raman microspectroscopy for cellular and subcellular analysis: towards in vitro high-content spectralomic analysis

Byrne¹,

Bonnier

Casey³

et al. 2018

Appl. Opt.

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In the confocal mode, Raman microspectroscopy can profile the biochemical content of biological cells at a subcellular level, and any changes to it by exogenous agents, such as therapeutic drugs or toxicants. As an exploration of the potential of the technique as a high-content, label-free analysis technique, this report reviews work to monitor the spectroscopic signatures associated with the uptake and response pathways of commercial chemotherapeutic agents and polymeric nanoparticles by human lung cells. It is demonstrated that the signatures are reproducible and characteristic of the cellular event, and can be used, for example, to identify the mode of action of the agent as well as the subsequent cell death pathway, and even mechanisms of cellular resistance. Data mining approaches are discussed and a spectralomics approach is proposed.

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Monitoring doxorubicin cellular uptake and trafficking using in vitro Raman microspectroscopy: short and long time exposure effects on lung cancer cell lines

Farhane¹,

Bonnier

Byrne³

2016

Anal Bioanal Chem

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Pentoxifylline as a modulator of anticancer drug doxorubicin. Part II: Reduction of doxorubicin DNA binding and alleviation of its biological effects

Cited by 23 publications

References 39 publications

Antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts

Antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts

Advancing Raman microspectroscopy for cellular and subcellular analysis: towards in vitro high-content spectralomic analysis

Monitoring doxorubicin cellular uptake and trafficking using in vitro Raman microspectroscopy: short and long time exposure effects on lung cancer cell lines

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