In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

Mylonaki, Efrosyni; Manika, Κaterina; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, D.

doi:10.1016/j.mrfmmm.2012.10.002

Cited by 10 publications

(8 citation statements)

References 29 publications

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“…The data demonstrated in this work indicates that these pro-inflammatory cytokines play a major role in hematologic malignancies [61,91], although they have been observed to play an important role in the modulation of the tumor microenvironment in other malignancies such; renal carcinoma [61], melanoma [60] and lung carcinoma [92]. Immunotherapy has been efficiently used in lung cancer [93,94], however; it seems that this treatment modality has a special role as a blocker for early chromosome instability and afterwards as therapy. Cytokines could be also used as biomarkers for survival [95].…”

Section: Discussionmentioning

confidence: 79%

Interleukin-8 and Interleukin-17 for Cancer

Zarogoulidis¹,

Katsikogianni²,

Tsiouda³

et al. 2014

Cancer Investigation

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103

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Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer.

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Section: Discussionmentioning

confidence: 79%

Interleukin-8 and Interleukin-17 for Cancer

Zarogoulidis¹,

Katsikogianni²,

Tsiouda³

et al. 2014

Cancer Investigation

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103

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“…), whereas others have been used as therapeutic agents, and recently have been marked differentiative properties on tumor cells. 25 , 26 The best known of these natural alkaloids are theophylline (TH, 1,3-dimethylxanthine), theobromine (3,7-dimethylxanthine), aminophylline (1,3-dimethyl-7H-purine-2,6-dione) and caffeine (1,3,7-trimethylxanthine). Theophylline, also known as 1,3-dimethylxanthine is being used as a bronchodilator drug in pulmonary diseases such as asthma or chronic pulmonary obstructive disease (COPD).…”

Section: Introductionmentioning

confidence: 99%

Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer

et al. 2017

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Purpose: Lung cancer remains the leading cause of cancer-related deaths worldwide and novel therapeutic approaches targeting crucial pathways are urgently needed to improve its treatment. Differentiation-based therapeutics (Methylxanthines) and phosphodiesterase inhibitors (type 4 and 5), have been implicated in cancer treatment. Our objectives were to capture any potential anti-tumor effect of these drug combinations with chemotherapeutic agents in vitro.Methods: Theophylline as Methylxanthines, Roflumilast as phosphodiesterase type 4 (PDE4) inhibitor and Sildenafil as phosphodiesterase type 5 (PDE5) inhibitor are the drugs that we combined with the chemotherapeutic agents (Docetaxel, Cisplatin and Carboplatin) in vitro. Lung cancer cell lines (NCI-H1048-Small cell lung cancer-SCLC, A549- Non-small cell lung cancer-NSCLC) were purchased from ATCC LGC Standards. At indicated time-point, following 24h and 48h incubation, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Statistical analysis was performed by GraphPad Prism.Results: In SCLC, following 48h incubation, platinum combinations of carboplatin with roflumilast and sildenafil (p<0.001) and carboplatin with theophylline and sildenafil showed increased apoptosis when compared to carboplatin alone. Concerning the combinations of cisplatin, when combined with roflumilast, theophylline and sildenafil appeared with increased apoptosis of that alone (p<0.001, 24h and 48h incubation). In NSCLC, the 24h incubation was not enough to induce satisfactory apoptosis, except for the combination of cisplatin with roflumilast and theophylline (p<0.05) when compared to cisplatin alone. However, following 48h incubation, carboplatin plus sildenafil, carboplatin plus sildenafil, theophylline and roflumilast showed more cytotoxicity when compared to carboplatin alone (p<0.001). Docetaxel combinations showed no statistically significant results.Conclusion: The synergistic effect of PDE inhibitors with platinum-based agents has been demonstrated in lung cancer. Our suggestion is that these combinations could be used as additive and maintenance treatment in combination to antineoplastic agents in lung cancer patients.

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“…Aminophylline (AM) is a complex of the bronchodilator theophylline [1]. AM has been used for treating asthma over 70 years [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Aminophylline has multiple potential beneficial actions in asthma, e.g., bronchial muscle relaxation, improvement in diaphragm contractility, diuretic function, and so on [4]. In addition, AM is a nonselective adenosine receptor antagonist and a phosphodiesterase (PDE) inhibitor that elevates intracellular levels of cyclic AMP (cAMP) [1]. High intracellular levels of cAMP can lead to the expansion of the smooth muscle [5].…”

Section: Introductionmentioning

confidence: 99%

The influence of aminophylline on the nanostructure and nanomechanics of T lymphocytes: an AFM study

Huang

Zhou

2014

Nanoscale Res Lett

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Although much progress has been made in the illustration of the mechanism of aminophylline (AM) treating asthma, there is no data about its effect on the nanostructure and nanomechanics of T lymphocytes. Here, we presented atomic force spectroscopy (AFM)-based investigations at the nanoscale level to address the above fundamental biophysical questions. As increasing AM treatment time, T lymphocytes' volume nearly double increased and then decreased. The changes of nanostructural features of the cell membrane, i.e., mean height of particles, root-mean-square roughness (Rq), crack and fragment appearance, increased with AM treatment time. T lymphocytes were completely destroyed with 96-h treatment, and they existed in the form of small fragments. Analysis of force-distance curves showed that the adhesion force of cell surface decreased significantly with the increase of AM treatment time, while the cell stiffness increased firstly and then decreased. These changes were closely correlated to the characteristics and process of cell oncosis. In total, these quantitative and qualitative changes of T lymphocytes' structure and nanomechanical properties suggested that AM could induce T lymphocyte oncosis to exert anti-inflammatory effects for treating asthma. These findings provide new insights into the T lymphocyte oncosis and the anti-inflammatory mechanism and immune regulation actions of AM.

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In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

Cited by 10 publications

References 29 publications

Interleukin-8 and Interleukin-17 for Cancer

Interleukin-8 and Interleukin-17 for Cancer

Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer

The influence of aminophylline on the nanostructure and nanomechanics of T lymphocytes: an AFM study

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