Cellular Physiology and Biochemistry

Our medical research library holds 10 studies published in Cellular Physiology and Biochemistry (2012–2021). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 10 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Cell Physiol Biochem Press GmbH & Co KG
• Published: 1991 to the present, Germany
• Language: English
• ISSN: 1015-8987 (print), 1421-9778 (electronic)
• Its record in the NLM Catalog

2020s

• Adaption of Lung Fibroblasts to Fluoro-Edenite Fibers: Evaluation of Molecular and Physiological Dynamics. A.C.E. Graziano, C. Ledda, C. Loreto, et al. 2021;55(3):327-343. PubMed · Publisher

  Abstract

  Background/Aims: The fluoro-edenite fibrous amphibole was identified as an environmental pollutant associate to risk of carcinogenicity. In Sicily (Italy), it represents a public health issue because fluoro-edenite fibers are present in the soil of Biancavilla, a town located on the south-west slopes of the volcano Etna. Since the relationship between exposure to fluoro-edenite and the onset of lung disorders have been documented, in vitro studies were performed to clarify the mechanisms of damage, but most aspects remain unknown. Here, we focus on the effects of mineral fibers in a primary culture of lung fibroblasts. We supposed that the cells react to fluoro-edenite exposure by establishing a process of adaption that could modify their metabolic activity, their proliferation, and their physiological functions, as the production of extracellular matrix (ECM) components.

  Methods: To verify our hypothesis, we used immunofluorescence, cell proliferation, senescence, apoptosis, scratch, Western blot, Reverse transcription-polymerase chain reaction (RT-PCR), and evaluation of extracellular matrix components assays.

  Results: Results demonstrated that lung fibroblasts react to fluoro-edenite by a down-regulation of mitochondrial activity, a reduction of cell growth and migration, and a resistance to apoptosis. These elements suggested the induction of a premature senescent phenotype that was confirmed by senescence-associated beta-galactosidase (SA-β-Gal) activity, and by the analysis of ECM elements. We found an unbalance of collagens ratio, and changes in matrix metalloproteinase3 production and release.

  Conclusion: Our data suggest that fluoro-edenite-induced senescence of lung fibroblasts could be an early and underestimated step that may drive fibroblasts toward a fibrotic and carcinogenic phenotype.

  © Copyright by the Author(s). Published by Cell Physiol Biochem Press.

2010s

• Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole-Genome Sequencing. S. Zhang, Q. Zhang, Q. Sun, et al. 2018;45(1):163-174. PubMed · Publisher

  Abstract

  Background/Aims: Malignant mesothelioma of the tunica vaginalis testis is a rare and lethal disease. The genomic characteristics and genetic changes of tumor cells during the progression of this disease are unknown.

  Methods: we performed whole-genome sequencing of four successive tumor samples derived from surgery and a blood sample in a single patient.

  Results: All tumors were found to have significant C-to-T and T-to-C mutations, and amplification of copy number in chromosomes 1 and 12 were notified in all tumor samples. Subclone analysis revealed a parallel evolution of the tumor in this patient. We also identified some mutations in mesothelioma-associated genes such as KIF25, AHNAK, and PRDM2.

  Conclusions: The results showed a comprehensive genomic change in malignant mesothelioma of the tunica vaginalis testis and provide a better understanding of the clonal evolution during tumor recurrence and metastasis.

  © 2018 The Author(s). Published by S. Karger AG, Basel.

• Adenosine deaminase inhibitor EHNA exhibits a potent anticancer effect against malignant pleural mesothelioma. Y. Nakajima, T. Kanno, T. Nagaya, et al. 2015;35(1):51-60. PubMed · Publisher

  Abstract

  Background/Aims: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor and an effective therapy has been little provided as yet. The present study investigated the possibility for the adenosine deaminase (ADA) inhibitor EHNA as a target of MPM treatment.

  Methods: MTT assay, TUNEL staining, monitoring of intracellular adenosine concentrations, and Western blotting were carried out in cultured human MPM cell lines without and with knocking-down ADA. The in vivo effect of EHNA was assessed in mice inoculated with NCI-H2052 MPM cells.

  Results: EHNA induced apoptosis of human MPM cell lines in a concentration (0.01-1 mM)- and treatment time (24-48 h)-dependent manner, but such effect was not obtained with another ADA inhibitor pentostatin. EHNA increased intracellular adenosine concentrations in a treatment time (3-9 h)-dependent manner. EHNA-induced apoptosis of MPM cells was mimicked by knocking-down ADA, and the effect was neutralized by the adenosine kinase inhibitor ABT-702. EHNA clearly suppressed tumor growth in mice inoculated with NCI-H2052 MPM cells.

  Conclusion: The results of the present study show that EHNA induces apoptosis of MPM cells by increasing intracellular adenosine concentrations, to convert to AMP, and effectively prevents MPM cell proliferation. This suggests that EHNA may be useful for treatment of the tragic neoplasm MPM.

  © 2015 S. Karger AG, Basel.

• Phosphatidylinositol Induces Caspase-Independent Apoptosis of Malignant Pleural Mesothelioma Cells by Accumulating AIF in the Nucleus. S. Kanemura, A. Tsuchiya, T. Kanno, et al. 2015;36(3):1037-48. PubMed · Publisher

  Abstract

  Background/Aims: Phosphatidylinositol (PI) regulates a variety of cell processes. The present study investigated the antitumor action of 1,2-dioleoyl-sn-glycero-3-phospho-(1'-myo-inositol)(DOPI) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-myo-inositol)(DPPI) on human malignant pleural mesothelioma (MPM) cell lines such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells.

  Methods: MTT assay, TUNEL staining, flow cytometry using propidium iodide (PI) and annexin V (AV), enzymatic caspase assay, and nuclear staining using DAPI were carried out, and mitochondrial membrane potentials and intracellular distribution of apoptosis-inducing factor (AIF) were monitored in cells with and without the siRNA silencing the Bid-targeted gene.

  Results: Both DOPI and DPPI reduced cell viability for all the investigated MPM cell lines in a concentration (0.01-100 µM)-dependent manner. DOPI and DPPI significantly increased TUNEL-positive cells and the population of PI-negative/AV-positive and PI-positive/AV-positive cells, corresponding to early apoptosis and late apoptosis/secondary necrosis, respectively. DOPI and DPPI perturbed mitochondrial membrane potentials in MSTO-211H cells, but no significant activation of caspase-3, -4, -8, and -9 was obtained. DOPI and DPPI upregulated expression of Bid in MSTO-211H cells. DOPI and DPPI significantly increased nuclear localization of AIF without affecting expression of the mRNAs and proteins in MSTO-211H cells, which was inhibited by knocking-down Bid. In the DAPI staining, nuclear fragmentation and condensation were found.

  Conclusion: The results of the present study indicate that DOPI and DPPI facilitate Bid-mediated AIF release from the mitochondria, to accumulate AIF in the nucleus and induce caspase-independent apoptosis of MPM cells.

  © 2015 S. Karger AG, Basel.

• Crosstalk between PI3 kinase/PDK1/Akt/Rac1 and Ras/Raf/MEK/ERK pathways downstream PDGF receptor. E.T. Niba, H. Nagaya, T. Kanno, et al. 2013;31(6):905-13. PubMed · Publisher

  Abstract

  Background/Aims: Our earlier studies suggested crosstalk between IRS/PI3 kinase/PDK1/Akt/Rac1/ROCK and (Shc2/Grb2/SOS)/Ras/Raf/MEK/ERK pathways downstream PDGF-ββ receptor responsible for chemotaxis and proliferation of malignant mesothelioma cells. The present study was conducted to obtain evidence for this.

  Methods: To assess activation of Akt, MEK, and ERK, Western blotting was carried out on MSTO-211H malignant mesothelioma cells using antibodies against phospho-Thr308-Akt, phopho-Ser473-Akt, Akt, phospho-MEK, MEK, phopho-ERK1/2, and ERK1/2. To knock-down Akt, PI3 kinase, PDK1, and Rac1, siRNAs silencing each-targeted gene were constructed and transfected into cells. To monitor Rac1 activity, FRET monitoring was carried out on living and fixed cells.

  Results: ERK was activated under the basal conditions in MSTO-211H cells, and the activation was prevented by inhibitors for PI3 kinase, PDK1, Akt, and Rac1 or by knocking-down PI3 kinase, PDK1, Akt, and Rac1. Akt was also activated under the basal conditions, and the activation was suppressed by a MEK inhibitor and an ERK1/2 inhibitor. In the FRET analysis, Rac1 was activated under the basal conditions, and the activation was inhibited by a MEK inhibitor and an ERK1/2 inhibitor.

  Conclusion: The results of the present study show that ERK could be activated by PI3 kinase, PDK1, Akt, and Rac1 and that alternatively, Akt and Rac1 could be activated by MEK and ERK in MSTO-211H cells.

  Copyright © 2013 S. Karger AG, Basel.

• Free fatty acids inhibit protein tyrosine phosphatase 1B and activate Akt. E. Shibata, T. Kanno, A. Tsuchiya, et al. 2013;32(4):871-9. PubMed · Publisher

  Abstract

  Background/Aims: Accumulating evidence has suggested that free fatty acids (FFAs) interact with protein kinases and protein phosphatases. The present study examined the effect of FFAs on protein phosphatases and Akt.

  Methods: Activities of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A), and protein tyrosine phosphatase 1B (PTP1B) were assayed under the cell-free conditions. Phosphorylation of Akt was monitored in MSTO-211H human malignant pleural mesothelioma cells without and with knocking-down phosphatidylinositol 3 kinase (PI3K) or 3-phosphoinositide-dependent protein kinase-1 (PDK1).

  Results: In the cell-free assay, unsaturated FFAs (uFFAs) such as oleic, linoleic and linolenic acid and saturated FFAs (sFFAs) such as stearic, palmitic, myristic, and behenic acid markedly reduced PTP1B activity, with the potential for uFFAs greater than that for sFFAs. All the investigated sFFAs inhibited PP2A activity, but otherwise no inhibition was obtained with uFFAs. Both uFFAs and sFFAs had no effect on PP1 activity. Oleic acid phosphorylated Akt both on Thr308 and Ser473, while stearic acid phosphorylated Akt on Thr308 alone. The effects of oleic and stearic acid on Akt phosphorylation were abrogated by the PI3K inhibitor wortmannin or the PDK1 inhibitor BX912 and also by knocking-down PI3K or PDK1.

  Conclusion: The results of the present study indicate that uFFAs and sFFAs could activate Akt through a pathway along a PI3K/PDK1/Akt axis in association with PTP1B inhibition.

  © 2013 S. Karger AG, Basel

• AMP converted from intracellularly transported adenosine upregulates p53 expression to induce malignant pleural mesothelioma cell apoptosis. Y. Nogi, T. Kanno, T. Nakano, et al. 2012;30(1):61-74. PubMed · Publisher

  Abstract

  Background/Aims: The present study investigated adenosine-induced apoptosis in human malignant pleural mesothelioma cells.

  Methods: MTT assay, TUNEL staining, flow cytometry using propidium iodide and annexin V-FITC, real-time RT-PCR, Western blotting, and assay of caspase-3, -8, and -9 activities were carried out using malignant pleural mesothelioma cell lines such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells, and p53 or A(3) adenosine receptor was knocked-down by transfecting each siRNA into cells.

  Results: Adenosine induced apoptosis in all the malignant pleural mesothelioma cells used here, independently of caspase activation. The adenosine effect was prevented by the adenosine transporter inhibitor dipyridamole, the adenosine kinase inhibitor ABT-702, or the A(3) adenosine receptor inhibitor MRS1191. Adenosine upregulated expression of the p53 mRNA and protein, that is abolished by ABT-702, but not by knocking-down A(3) adenosine receptor. Adenosine-induced apoptosis in NCI-H28 cells was significantly inhibited by knocking-down p53 and in part by knocking-down A(3) adenosine receptor.

  Conclusion: The results of the present study show that AMP converted from intracellularly transported adenosine upregulates p53 expression to induce caspase-independent apoptosis in malignant pleural mesothelioma cells and that A(3) adenosine receptor also participates partially in the apoptosis by the different mechanism.

  Copyright © 2012 S. Karger AG, Basel.

• Mesothelioma cell proliferation through autocrine activation of PDGF-ββ receptor. M. Honda, T. Kanno, Y. Fujita, et al. 2012;29(5-6):667-74. PubMed · Publisher

  Abstract

  Background/Aims: Growth factors play a critical role in proliferation for a variety of cancer cells. The present study was conducted to understand the signaling cascades underlying PDGF-D/PDGF-ββ receptor-mediated proliferation of mesothelioma cells.

  Methods: Cell growth and cell cycle were analyzed in human non-malignant Met5A cells and malignant mesothelioma cells such as MSTO-211H, NCI-H28, NCI-H2052, and NCI-H2452 cells.

  Results: Growth of all the cells used here was not affected by PDGF-D, regardless of concentrations (1-30 ng/ml) or treatment time (48-72 h). Spontaneous growth of those cells was significantly inhibited by knocking-down PDGFD or PDGF-ββ receptor, without affecting cell cycling. The cell growth was significantly inhibited by the Akt inhibitor MK2206 and the ROCK inhibitor Y27632 for all the cell types, by the PDK1 inhibitor BX912 for NCI-H28 cells alone, and by the Rac1 inhibitor NSC23766 for NCI-H2052 cells alone, while the PI3 kinase inhibitor wortmannin had no effect. The cell growth, alternatively, was significantly attenuated by MAP kinase kinase inhibitor PD98059 or the ERK1/2 inhibitor FR180204 for all the cell types.

  Conclusion: The results of the present study show that PDGF-D promotes mesothelioma cell proliferation by targeting ROCK or MAP kinase through autocrine activation of PDGF-ββ receptor.

  Copyright © 2012 S. Karger AG, Basel.

• PDGF-D/PDGF-ββ receptor-regulated chemotaxis of malignant mesothelioma cells. A. Okada, T. Yaguchi, T. Kanno, et al. 2012;29(1-2):241-50. PubMed · Publisher

  Abstract

  Background/Aims: Our earlier study suggested that platelet-derived growth factor (PDGF)- ββ receptor regulates chemotaxis of human malignant mesothelioma cells such as MSTO-211H, NCIH-2052, NCIH-2452, and NCIH-28 cells, but not non-malignant Met5A cells. The present study was designed to gain further insight into the PDGF-ββ receptor signals underlying the chemotaxis.

  Methods: PDGF-D secreted from cells, activation of Akt and ERK, and cell migration were monitored for cells with and without knocking-down PDGF-ββ receptor.

  Results: FBS significantly stimulated PDGF-D secretion from malignant mesothelioma cells, but not Met5A cells. PDGF-D activated Akt and ERK in both the non-malignant and malignant cells. PDGF-D significantly facilitated migration of malignant mesothelioma cells, but not Met5A cells, with the extent varying among the cell types. The facilitatory action of PDGF-D was clearly prevented by knocking-down PDGF-ββ receptor or inhibitors of PI3 kinase, PDK1, Akt, Rac1, ROCK, and MEK.

  Conclusion: The results of the present study indicate that PDGF-D promotes malignant mesothelioma cell chemotaxis through PDGF-ββ receptor signaling pathways along a PI3 kinase/PDK1/Akt/Rac1/ROCK axis and relevant to ERK activation.

  Copyright © 2012 S. Karger AG, Basel.

• Sphingosine suppresses mesothelioma cell proliferation by inhibiting PKC-δ and inducing cell cycle arrest at the G(0)/G(1) phase. H. Okuwa, T. Kanno, Y. Fujita, et al. 2012;30(4):995-1004. PubMed · Publisher

  Abstract

  Background/Aims: Sphingosine regulates cellular differentiation, cell growth, and apoptosis. The present study aimed at understanding sphingosine-regulated mesothelioma cell proliferation.

  Methods: Human malignant mesothelioma cells such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells were cultured. The siRNA to silence the protein kinase C (PKC)-δ-targeted gene was constructed and transfected into cells. MTT assay, cell cycle analysis using a flow cytometry, and cell-free PKC-δ assay were carried out.

  Results: For all the cell types sphingosine inhibited cell growth in a concentration (1-100 µM)-dependent manner. The sphingosine effect was not prevented by rottlerin, an inhibitor of protein kinase C-δ (PKC-δ); conversely, rottlerin further enhanced the sphingosine effect or rottlerin suppressed mesothelioma cell growth without sphingosine. In the cell-free PKC assay, sphingosine attenuated PKC-δ activity. Knocking-down PKC-δ induced cell cycle arrest at the G0/G1 phase and inhibited cell growth.

  Conclusion: The results of the present study show that sphingosine suppressed mesothelioma cell proliferation by inhibiting PKC-δ, to induce cell cycle arrest at the G0/G1 phase.

  Copyright © 2012 S. Karger AG, Basel.

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