The effect of cisplatin on human larynx carcinoma cell motility

Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
Folia Histochemica et Cytobiologica (Impact Factor: 1.36). 02/2009; 47(1):75-9. DOI: 10.2478/v10042-009-0022-2
Source: PubMed


Head and neck tumors are one of the major public health problem all over the world. Cellular response of larynx carcinoma to cisplatin (CDDP) chemotherapy occurs both in cell-interdependent and cell-autonomous pathways. In the first pathway, cytotoxic signal transduction is mediated via gap-junctional intercellular communication (GIJC). CDDP also influence tumor cell migration.The aim of this study was the analysis of the effect of CDDP (0.5 microg/ml and 1.5 microg/ml) on the gap-junction intercellular communication and motility, respectively, in two new cell cultures (RK33 and RK45) derived from human larynx carcinoma. The migration of RK45 cell line was slightly inhibited and RK33 not affected after the incubation with CDDP. Tumor cells incubation with CDDP resulted in farther LY migration through neighboring cells beyond monolayer wound than in control cultures.In conclusion, there is a relationship between intercellular communication via gap junctions and motility of laryngeal tumor cells after CDDP application.

Full-text preview

Available from:
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colon carcinoma invasiveness is a process involving cell-cell and cell-matrix alterations, local proteolysis of the ECM (extracellular matrix) or changes in cytokine and growth factor levels. In order to evaluate the role of TGF-beta1 (transforming growth factor-beta1) and small G protein RhoA in tumour progression, the influence of TGF-beta1 treatment or RhoA-associated kinase inhibitor on the production of NO (nitric oxide) and MMP-2 and MMP-9 (metalloproteinases-2 and -9) was analysed in three human colon adenocarcinoma cell lines (HT29, LS180, SW948) representing different stages of tumour development. All the tested cell lines produced low amounts of MMP-2 and MMP-9. rhTGF-beta1 and the synthetic Rho kinase inhibitor (Y-27632) decreased MMP-2 secretion by colon cancer cells, especially in the most advanced stage of colon cancer. rhTGF-beta1 decreased NO secretion by cells, while Y-27632 had no effect on it. Immunoblotting with anti-RhoA antibodies followed by densitometry revealed that RhoA levels were slightly increased after incubation of colon carcinoma cells (SW948) with rhTGF-beta1. rhTGF-beta1 induced alpha-smooth muscle actin (alpha-SMA) expression, especially in high Duke's grade of colon cancer, while Y-27632 blocked it. Summing up, in colon carcinoma cells, TGF-beta1 and RhoA protein may regulate tumour invasiveness measured as MMP, NO and alpha-SMA expression or assayed using motility data and may be a good target for cancer therapy.
    No preview · Article · Oct 2009 · Cell Biology International
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cellular responses to DNA-damaging agents involve the activation of various DNA damage signaling and transduction pathways. Using quantitative and high-resolution tandem mass spectrometry, we determined global changes in protein level and phosphorylation site profiles following treatment of SILAC (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected. Although the ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) consensus sequence (S/T-Q motif) was significantly overrepresented among hyperphosphorylated peptides, about half of the >2-fold-upregulated phosphorylation sites based on the consensus sequence were not direct substrates of ATM and ATR. Eleven protein kinases mainly belonging to the mitogen-activated protein kinase (MAPK) family were identified as being regulated in their kinase domain activation loop. The biological importance of three of these kinases (cyclin-dependent kinase 7 [CDK7], Plk1, and KPCD1) in the protection against cisplatin-induced cytotoxicity was demonstrated by small interfering RNA (siRNA)-mediated knockdown. Our results indicate that the cellular response to cisplatin involves a variety of kinases and phosphatases not only acting in the nucleus but also regulating cytoplasmic targets, resulting in extensive cytoskeletal rearrangements. Integration of transcriptomic and proteomic data revealed a poor correlation between changes in the relative levels of transcripts and their corresponding proteins, but a large overlap in affected pathways at the levels of mRNA, protein, and phosphoprotein. This study provides an integrated view of pathways activated by genotoxic stress and deciphers kinases that play a pivotal role in regulating cellular processes other than the DNA damage response.
    Full-text · Article · Dec 2011 · Molecular and Cellular Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the influence of cisplatin and an extremely low frequency electromagnetic field (ELF-EMF) on antioxidant enzyme activity and the lipid peroxidation ratio, as well as the level of DNA damage and reactive oxygen species (ROS) production in AT478 carcinoma cells. Cells were cultured for 24 and 72 h in culture medium with cisplatin. Additionally, the cells were irradiated with 50 Hz/1 mT ELF-EMF for 16 min using a solenoid as a source of the ELF-EMF. The amount of ROS, superoxide dismutase (SOD) isoenzyme activity, glutathione peroxidase (GSH-Px) activity, DNA damage, and malondialdehyde (MDA) levels were assessed. Cells that were exposed to cisplatin exhibited a significant increase in ROS and antioxidant enzyme activity. The addition of ELF-EMF exposure to cisplatin treatment resulted in decreased ROS levels and antioxidant enzyme activity. A significant reduction in MDA concentrations was observed in all of the study groups, with the greatest decrease associated with treatment by both cisplatin and ELF-EMF. Cisplatin induced the most severe DNA damage; however, when cells were also irradiated with ELF-EMF, less DNA damage occurred. Exposure to ELF-EMF alone resulted in an increase in DNA damage compared to control cells. ELF-EMF lessened the effects of oxidative stress and DNA damage that were induced by cisplatin; however, ELF-EMF alone was a mild oxidative stressor and DNA damage inducer. We speculate that ELF-EMF exerts differential effects depending on the exogenous conditions. This information may be of value for appraising the pathophysiologic consequences of exposure to ELF-EMF. Bioelectromagnetics. © 2012 Wiley Periodicals, Inc.
    Full-text · Article · Dec 2012 · Bioelectromagnetics