scholarly journals Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro

2021 ◽  
Vol 11 ◽  
Author(s):  
Tibor Hajdú ◽  
Patrik Kovács ◽  
Emese Zsigrai ◽  
Roland Takács ◽  
Judit Vágó ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
The Body ◽  
Melanoma Progression ◽  
Pituitary Adenylate Cyclase ◽  
Pacap Receptors ◽  
Melanoma Cell Lines

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide which is distributed throughout the body. PACAP influences development of various tissues and exerts protective function during cellular stress and in some tumour formation. No evidence is available on its role in neural crest derived melanocytes and its malignant transformation into melanoma. Expression of PACAP receptors was examined in human skin samples, melanoma lesions and in a primary melanocyte cell culture. A2058 and WM35 melanoma cell lines, representing two different stages of melanoma progression, were used to investigate the effects of PACAP. PAC1 receptor was identified in melanocytes in vivo and in vitro and in melanoma cell lines as well as in melanoma lesions. PACAP administration did not alter viability but decreased proliferation of melanoma cells. With live imaging random motility, average speed, vectorial distance and maximum distance of migration of cells were reduced upon PACAP treatment. PACAP administration did not alter viability but decreased proliferation capacity of melanoma cells. On the other hand, PACAP administration decreased the migration of melanoma cell lines towards fibronectin chemoattractant in the Boyden chamber. Furthermore, the presence of the neuropeptide inhibited the invasion capability of melanoma cell lines in Matrigel chambers. In summary, we provide evidence that PACAP receptors are expressed in melanocytes and in melanoma cells. Our results also prove that various aspects of the cellular motility were inhibited by this neuropeptide. On the basis of these results, we propose PACAP signalling as a possible target in melanoma progression.

Secretion of Cytokines by Human Choroidal Melanoma Cells and Skin Melanoma Cell Lines in vitro

1998 ◽  
Vol 30 (3) ◽  
pp. 189-194 ◽  
Author(s):  
Volker Enzmann ◽  
Frank Faude ◽  
Leon Kohen ◽  
Peter Wiedemann
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Choroidal Melanoma ◽  
Melanoma Cells ◽  
Skin Melanoma ◽  
Melanoma Cell Lines

Recombinant arginase as a novel anti-melanoma agent

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12032-12032 ◽  
Author(s):  
E. C. Hsueh ◽  
S. Knebel ◽  
I. Collier ◽  
M. Kadze ◽  
C. Hsueh ◽  
...  
Keyword(s):  
Real Time ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Large Scale ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Subtilis Strain ◽  
Argininosuccinate Synthetase ◽  
Melanoma Cell Lines

12032 Background: BCT-100 is a recombinant arginase comprised of 329 amino acid residues. Arginase converts arginine to urea and ornithine. Previous studies suggested that melanoma cells were auxotrophic for arginine due to absence of argininosuccinate synthetase (ASS) expression. Thus, we hypothesized that recombinant arginase, BCT-100, is cytotoxic to human melanoma cells and its cytotoxicity correlates with absence of ASS expression. Methods: BCT-100 pegylated recombinant human arginase was manufactured by large scale fermentation of a recombinant B. subtilis strain LLC101 encoded with a human arginase gene. Following fermentation, the recombinant protein was extracted, purified, pegylated, and ultra-dialyzed. Ten established human melanoma cell lines were used. Cells were grown to 90% confluence, harvested, and plated at 104 cells per well in a 96-well plate and co-cultured with increasing concentrations of pegylated BCT-100 for 72 hours. CellTiter 96 Aqueous Non-radioactive Cell Proliferation Assay (Promega, Madison, WI) was used to measure percent viability, with absorbances measured at 490 nm. Total cellular RNA was isolated from established melanoma cell lines converted to cDNA at a concentration of 5 ng/ul. Quantitative real time polymerase chain reaction was performed on a 7300 Real Time PCR System, using Gene Expression Assays for ASS and GAPDH (Applied Biosystems). 10,000 fold standard curves were generated for all samples using GAPDH expression. Results: All ten cell lines demonstrated decreased viability as concentrations of BCT-100 increased. Average IC50 value was 0.11 IU/ml. Eight of the 10 cells lines have IC50 values < 0.1 IU/ml. Of the 8 cell lines with IC50< 0.1 IU/ml, all of them have low or undetectable ASS expression using quantitative RT-PCR. Of the 2cell lines with IC50 > 0.1 IU/ml, ASS expression was detected in 1 of 2. Conclusions: Arginine depletion with recombinant arginase, BCT-100, was cytotoxic to melanoma cells in vitro. The cytotoxic effect of BCT-100 on melanoma cells correlated with expression of argininosuccinate synthetase. BCT-100 is a promising novel agent for treatment of melanoma. Further in vivo experiment with BCT-100 is ongoing. [Table: see text]

scholarly journals Synergy, Additivity, and Antagonism between Cisplatin and Selected Coumarins in Human Melanoma Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 537
Author(s):  
Paula Wróblewska-Łuczka ◽  
Aneta Grabarska ◽  
Magdalena Florek-Łuszczki ◽  
Zbigniew Plewa ◽  
Jarogniew J. Łuszczki
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Type I ◽  
Antiproliferative Effects ◽  
Isobolographic Analysis ◽  
Natural Substances ◽  
Additive Interactions ◽  
Melanoma Cell Lines

(1) Cisplatin (CDDP) is used in melanoma chemotherapy, but it has many side effects. Hence, the search for natural substances that can reduce the dose of CDDP, and CDDP-related toxicity, is highly desired. Coumarins have many biological properties, including anticancer and antiproliferative effects. (2) An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on two human melanoma cell lines (FM55P and FM55M2) examined the antitumor properties of CDDP and five naturally occurring coumarins (osthole, xanthotoxin, xanthotoxol, isopimpinellin, and imperatorin). The antiproliferative effects produced by combinations of CDDP with the coumarins were assessed using type I isobolographic analysis. (3) The most potent anticancer properties of coumarins were presented by osthole and xanthotoxol. These compounds were characterized by the lowest median inhibitory concentration (IC50) values relative to the FM55P and FM55M2 melanoma cells. Isobolographic analysis showed that for both melanoma cell lines, the combination of CDDP and osthole exerted synergistic and additive interactions, while the combination of CDDP and xanthotoxol exerted additive interactions. Combinations of CDDP with xanthotoxin, isopimpinellin, and imperatorin showed antagonistic and additive interactions in two melanoma cell lines. (4) The combination of CDDP and osthole was characterized by the most desirable synergistic interaction. Isobolographic analysis allows the selection of potential candidates for cancer drugs among natural substances.

scholarly journals Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib in NRAS-Mutant Melanoma Cell Lines

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2012
Author(s):  
Kathryn M. Appleton ◽  
Charuta C. Palsuledesai ◽  
Sean A. Misek ◽  
Maja Blake ◽  
Joseph Zagorski ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Therapeutic Potential ◽  
Mapk Pathway ◽  
Mek Inhibitor ◽  
Intrinsic Resistance ◽  
Primary Resistance ◽  
Induced Apoptosis ◽  
Melanoma Cell Lines

The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (≈50% BRAFV600 mutations and ≈30% NRAS mutations). While drugs targeting the MAPK pathway have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in patients with NRAS mutant melanomas in part due to their cytostatic effects and primary resistance. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to the MEK inhibitor, trametinib, in a panel of NRAS mutant melanoma cell lines. A combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in SK-Mel-147 cells, which are highly resistant to trametinib. These findings suggest a role of the Rho/MRTF-pathway in intrinsic trametinib resistance in a subset of NRAS mutant melanoma cell lines and highlight the therapeutic potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.

In vitro synergy of paclitaxel (Taxol) and vinorelbine (navelbine) against human melanoma cell lines

1997 ◽  
Vol 33 (3) ◽  
pp. 463-470 ◽  
Author(s):  
A. Photiou ◽  
P. Shah ◽  
L.K. Leong ◽  
J. Moss ◽  
S. Retsas
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Melanoma Cell Lines

scholarly journals Atorvastatin enhances the antitumor activity of tamoxifen in B16f10 mouse melanoma cell lines

2020 ◽  
Vol 25 (1) ◽  
pp. 83-91
Author(s):  
Maryam Malek ◽  
◽  
Maedeh Ghasemi ◽  
Golnaz Vaseghi ◽  
Ahmad Ghasemi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Mevalonate Pathway ◽  
Combined Therapy ◽  
Metastatic Malignant Melanoma ◽  
Mouse Melanoma ◽  
Melanoma Cancer ◽  
Mouse Melanoma Cell ◽  
Melanoma Cell Lines

Introduction: Tamoxifen has been used in the treatment of metastatic malignant melanoma more common with other agents in the combined therapy. Up-regulated activity of the mevalonate pathway has been shown in a range of different cancers. Atorvastatin is the most commonly used statin approved for cholesterol reduction by inhibiting the mevalonate pathway and has been shown to inhibit tumor growth. In the present study, we used atorvastatin and tamoxifen combination therapy on B16f10 mouse melanoma cell lines to study whether atorvastatin could increase the sensitivity of melanoma cells to the chemotherapeutic agent such as tamoxifen. Methods: The cell line was treated with different concentrations of tamoxifen and/or atorvastatin for 24 and 48h and the effects of treatment on p53 and RhoA were investigated using quantitative RT-PCR. Results: The combination of atorvastatin and tamoxifen resulted in a potentiation antitumor effect via up-regulation of p53 and down-regulation of RhoA expression against melanoma tumors in vitro. Furthermore, we demonstrated the combination of atorvastatin with tamoxifen could reduce tamoxifen dose to minimize possible detrimental side effects in melanoma. Conclusion: Our results suggested that atorvastatin as a combined therapy with tamoxifen may provide a new approach for improving the efficacy and treating against melanoma cancer but needs further exploration in clinical trials.

scholarly journals In vitro cell cytotoxicity profile and morphological response to polyoxometalate-stabilised gold nanoparticles

2016 ◽  
Vol 40 (2) ◽  
pp. 1039-1047 ◽  
Author(s):  
Isabel Maicas Gabas ◽  
Grazyna Stepien ◽  
María Moros ◽  
Scott G. Mitchell ◽  
Jesús M. de la Fuente
Keyword(s):  
Gold Nanoparticles ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Cell Cytotoxicity ◽  
Skin Melanoma ◽  
Morphological Response ◽  
Antiproliferative Action ◽  
Melanoma Cell Lines

Polyoxometalate-stabilised gold nanoparticles internalise in vast quantities into kidney epithelial and skin melanoma cell lines causing antiproliferative action on tumoural cells.

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