scholarly journals Dipeptidyl Peptidase IV as a Novel Prognostic Marker and Important Therapeutic Target in Melanoma

2021 ◽  
Author(s):  
Iwona Piatkowska-Chmiel ◽  
Monika Gawronska-Grzywacz ◽  
Magdalena Iwan ◽  
Dorota Natorska-Chomicka ◽  
Mariola Herbet ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Metastatic Potential ◽  
Inhibitory Effect ◽  
Short Term Treatment ◽  
Dpp Iv ◽  
Routine Identification ◽  
Melanoma Cell Lines

Abstract BackgroundThere is a lot of evidence which suggests that DPP IV level may correlate with a type of tumor cells, metastatic potential and prognosis for the patient. Bearing in mind that the melanomas are characterized by high heterogeneity and identification of specific phenotypes of cells allows for early and more effective therapy, the aim of our study was to check whether there is a correlation between the DPPIV and the metastatic potential of melanoma cell lines. Additionally, the aim of our research was to evaluate the anti-tumor potential of linagliptin and saxagliptin in melanoma cell lines as well as determining correlation between cytotoxicity of the drugs and DPP IV level. MethodsThe inhibitory effect of tested drugs on the cancer cell growth was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) while cell cycle analysis and apoptosis were performed using the NucleoCounter® NC-3000™ system (ChemoMetec, Denmark), following the instructions provided by the manufacturer. DPPIV release by cancer cells was measured by DPP4/CD26 ELISA assay kit for biological samples (Cloud-Clone Corp.,Wuhan,China). ResultsOur results showed that DPPIV overexpression promoted cell proliferation of melanoma cells. Our data showed that especially short term treatment with linagliptin is associated with not only decreased expression of DPPIV and inhibition of cell proliferation but also induction of cell cycle disruption and apoptosis in melanoma. ConclusionsThe routine identification of this glycoprotein in melanoma would be fundamental to assessing not only the risk of metastasis/disease progression but also selection of therapy and evaluation of its effectiveness.

Cell Proliferation Profile of Five Human Uveal Melanoma Cell Lines of Different Metastatic Potential

Pathobiology ◽  
2004 ◽  
Vol 71 (5) ◽  
pp. 241-245 ◽  
Author(s):  
Jean-Claude Marshall ◽  
Amanda L. Caissie ◽  
Sonia A. Callejo ◽  
Emilia Antecka ◽  
Miguel N. Burnier Jr.
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Uveal Melanoma ◽  
Melanoma Cell ◽  
Metastatic Potential ◽  
Uveal Melanoma Cell ◽  
Melanoma Cell Lines

Effect of celastrol on temozolomide cytotoxicity in melanoma cells and inhibition of NF-kB signaling

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9076-9076
Author(s):  
M. Chen ◽  
I. Osman ◽  
S. J. Orlow
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Natural Products ◽  
Natural Product ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Single Agent ◽  
Melanoma Cells ◽  
Cell Killing ◽  
Melanoma Cell Lines

9076 Background: Temozolomide (TMZ) exhibits clinical activity in the treatment of melanoma and glioblastoma, but response rates are low. Identification of agents that improve TMZ's efficacy and overcome resistance is of great interest. In this study, we have identified celastrol as a natural product that significantly enhances TMZ-induced cytotoxicity by testing a library of drugs and natural products for cytotoxic activity against glioma and melanoma cell lines and have examined its mechanism of action in melanoma cells. Methods: A preliminary screening of a library of 2000 drugs and natural products was performed and a short list of drugs was identified as able to enhance TMZ-induced cell killing in TMZ-resistant cancer cell lines. The effects of these compounds were further confirmed in five melanoma cell lines. A cell proliferation assay was used to compare growth inhibitory effects of single agent TMZ versus combination treatments. Synergy in inhibiting cell proliferation was assessed using combination-index methods. The expression of NF-kB, IkB, MAPK, and PARP were examined using Western blot analysis. The effect of treatments on the cell cycle was examined by flow cytometry. The localization of NF-kB in melanoma cells was evaluated through immunofluorescence microscopy. Results: Combining celastrol and TMZ synergistically inhibited cell proliferation, enhanced cell cycle arrest, and increased apoptosis in a series of melanoma cell lines, compared to treatment with TMZ alone. We further found that celastrol inhibited proteasome activity, TNF-α induced IkB phosphorylation and NF-kB translocation to the nucleus. Inhibition of NF-kB with siRNA mimicked the ability of celastrol to sensitize melanoma cells to TMZ-induced cell killing, suggesting inhibition of NF-kB was indeed involved in TMZ/celastrol-induced cytotoxicity. Furthermore, combination treatment induced phosphorylation of JNK. Conclusions: Our data suggest that combined use of TMZ with celastrol, a natural product derived from a vine extract that has been used orally in Chinese medicine for over a thousand years, may enhance the chemotherapeutic efficacy of TMZ in melanoma. No significant financial relationships to disclose.

scholarly journals Expression of cd44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential

1995 ◽  
Vol 64 (3) ◽  
pp. 182-188 ◽  
Author(s):  
Eveliene Manten-Horst ◽  
Erik H. J. Danen ◽  
Lia Smit ◽  
Margriet Snoek ◽  
I. Le Caroline Poole ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Cutaneous Melanoma ◽  
Splice Variants ◽  
Metastatic Potential ◽  
Melanoma Cell Lines

scholarly journals Expression ofnma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts

1996 ◽  
Vol 65 (4) ◽  
pp. 460-465 ◽  
Author(s):  
Winfried G. J. Degen ◽  
Marian A. J. Weterman ◽  
Jan J. M. van Groningen ◽  
Ine M. A. H. Cornelissen ◽  
Jolanda P. W. M. Lemmers ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Metastatic Potential ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Novel Gene ◽  
Melanoma Cell Lines

Chemosensitisation by poly(ADP-ribose) polymerase-1 (PARP-1) inhitor 5-aminoisoquinoline (5-AIQ) on various melanoma cell lines

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12019-12019 ◽  
Author(s):  
S. Radulovic ◽  
S. Bjelogrlic ◽  
Z. Todorovic ◽  
M. Prostran
Keyword(s):  
Cell Cycle ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Cell Cycle Progression ◽  
Single Agent ◽  
S Phase ◽  
G1 Arrest ◽  
Parp 1 ◽  
Melanoma Cell Lines

12019 Background: PARP-1 facilitates DNA strand brakes repair and PARP inhibitors were investigated as enhancers of chemoradiotherapy. We investigated whether 5-AIQ potentates the effect of doxorubicin (DOXO), cisplatin (CDDP) and paclitaxel (Ptx) on human (slow-growing) FemX and murine (fast-growing) B16 melanoma cell lines. Methods: Twenty-four hours after cells were seeded in 96 well plates, cytotoxic drugs and 5-AIQ were added to cell medium. For evaluation of single-agent activity, drugs were applied in concentration ranges as follows: CDDP (0.3–30 μM), DOXO (0.1–3 μM), Ptx (1–100 ηM), 5-AIQ (1–100 μM). 5-AIQ (3μM) was combined with CDDP (0.1, 0.3, 1 μM), DOXO (10, 3, 100 ηM), or Ptx (1, 3, 10 ηM). Incubation lasted for 72 hrs when SRB assay was utilized to determine individual and combine activity (interactions calculated with isobole method). For cell cycle analysis B16 cells were seeded on 6 well plates and treated with each drug alone and combinations, using the same concentrations as those for investigation of combine cytotoxic activity. Cell cycle was determined after 72 hrs, on FACS Calibur with propidium iodide dye. Results: 5-AIQ induced minimal changes in cell viability and cell cycle progression on both cell lines, compared to non-treated control. CDDP revealed high activity against FemX (IC50 = 2.85 μM) and B16 cells (IC50 = 8.84 μM), and G0/G1 arrest. In B16 cells 5-AIQ multiply enhanced CDDP’s activity with strong synergistic interaction and cells slightly driven to S phase. Synergism was also detected on B16 cells treated with combination of DOXO (IC50 = 0.2 μM on B16 and 0.89 μM on FemX) and 5-AIQ when DOXO was applied in low concentrations (10 and 30 ηM), while 5-AIQ did not interfere with cell cycle changes. Cytotoxicity of Ptx (IC50 = 6.16 ηM on B16 and <1 ηM on FemX) was stimulated only at higher concentrations. 5-AIQ stimulated G0/G1 and S phase arrest on B16 cells with Ptx of 3 and 10 ηM, respectively. In FemX cells, most of the interactions of 5-AIQ with CDDP, DOXO, and Ptx revealed as antagonistic. Conclusions: PARP-1 inhibitor 5-AIQ enhances cytotoxic activity of both DNA damaging and agents with different mechanism of action, but the effect varies between cell lines with different proliferation rate. No significant financial relationships to disclose.

scholarly journals Migration of highly aggressive melanoma cells on hyaluronic acid is associated with functional changes, increased turnover and shedding of CD44 receptors

1996 ◽  
Vol 109 (7) ◽  
pp. 1957-1964 ◽  
Author(s):  
M. Goebeler ◽  
D. Kaufmann ◽  
E.B. Brocker ◽  
C.E. Klein
Keyword(s):  
Hyaluronic Acid ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Malignant Tumors ◽  
Standard Form ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Functional Changes ◽  
Local Progression ◽  
Melanoma Cell Lines

Recent evidence indicates that CD44, a multifunctional adhesion receptor involved in cell-cell as well as in cell-matrix interactions, plays an important role in local progression and metastasis of malignant tumors. We have studied a set of human melanoma cell lines differing in their metastatic potential in nude mice as well as in normal melanocytes for changes in CD44 expression and function. All melanocytes and melanoma cell lines tested highly expressed the CD44 standard form (CD44s, 85 kDa) but variants at low levels only. With respect to one of the CD44-associated functions primarily involved in tumor progression we found that two highly metastatic tumor cell lines, MV3 and BLM, showed fivefold higher migration rates towards hyaluronate than melanomas with low metastatic potential and normal melanocytes. Moreover, the highly metastatic cell lines expressed four- to sixfold higher levels of the CD44 epitope involved in hyaluronic acid-binding (monoclonal antibody Hermes-1) than less aggressive melanomas and melanocytes. Hermes-1 efficiently blocked haptotaxis to hyaluronate, supporting the functional relevance of this epitope. In contrast, expression levels of other CD44s epitopes recognized by seven different anti-CD44 monoclonal antibodies were unchanged, suggesting that the migratory behaviour of the cells depends on the formation of the hyaluronate-binding Hermes-1 epitope rather than on the overall CD44s surface expression, which was virtually identical in all melanoma and melanocyte cell lines tested. Differences in the accessibility of the hyaluronate-binding epitope defined by Hermes-1 correlated with the phosphorylation state of CD44s, probably reflecting different activation states of the receptor. Furthermore, immunoprecipitation and pulse/chase studies revealed a three- to fivefold increase in CD44 synthesis in the highly aggressive melanoma cells as compared to the other cell lines and the melanocytes, indicating a reduction of CD44 half-life and up-regulation of turnover. Moreover, highly aggressive melanoma cell lines were found to shed significant amounts of CD44 from the cell surface and to secrete its ligand hyaluronic acid, which may refer to an “autocrine' mechanism mediating melanoma cell motility.

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