The effect of tricyclic antidepressants on cutaneous melanoma cell lines and primary cell cultures

2012 ◽  
Vol 23 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Katharine A. Parker ◽  
Sharon Glaysher ◽  
Jeremy Hurren ◽  
Louise A. Knight ◽  
Deidre McCormick ◽  
...  
1995 ◽  
Vol 64 (3) ◽  
pp. 182-188 ◽  
Author(s):  
Eveliene Manten-Horst ◽  
Erik H. J. Danen ◽  
Lia Smit ◽  
Margriet Snoek ◽  
I. Le Caroline Poole ◽  
...  

1986 ◽  
Vol 72 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Elisabetta Mattei ◽  
Andrea Delpino ◽  
Anna Maria Mileo ◽  
Umberto Ferrini

The induction of stress proteins was studied in two human and two murine melanoma cell lines. Exposure for 1 h to heat (42 °C), to ethanol (6%), to arsenate (100 μM) and to disulfiram (50 μM) induced the expression of SPs with apparent molecular weights of 100, 86, 70-72 and 24-26 Kd. Quantitation of the single SPs indicated that the basal level as well as the enhanced synthesis following the various stressors were different in each cell line. The induction of the 100 Kd species occurred in only one murine melanoma and not in the others. The 86 and in particular the 70-72 Kd species were the most prominent groups, whereas the 24-26 SPs were induced only following arsenate and disulfiram exposure in the three melanoma cell lines. In one of the murine melanomas, the expression of SPs was markedly reduced compared to the other cell lines. No definite specific patterns of SP expression could be identified in tumors of the same histologic type.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 928 ◽  
Author(s):  
Andrea Abate ◽  
Elisa Rossini ◽  
Sara Anna Bonini ◽  
Martina Fragni ◽  
Deborah Cosentini ◽  
...  

Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy including etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Evidence indicates that ACC seems to be sensitive to alkylating agents. Trabectedin is an anti-tumor drug that acts as an alkylating agent with a complex mechanism of action. Here, we investigated whether trabectedin could exert a cytotoxic activity in in vitro cell models of ACC. Cell viability was evaluated by MTT assay on ACC cell lines and primary cell cultures. The gene expression was evaluated by q-RT-PCR, while protein expression and localization were studied by Western blot and immunocytochemistry. Combination experiments were performed to evaluate their interaction on ACC cell line viability. Trabectedin demonstrated high cytotoxicity at sub-nanomolar concentrations in ACC cell lines and patient-derived primary cell cultures. The drug was able to reduce /β catenin nuclear localization, although it is unclear whether this effect is involved in the observed cytotoxicity. Trabectedin/mitotane combination exerted a synergic cytotoxic effect in NCI-H295R cells. Trabectedin has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of trabectedin with mitotane provides the rationale for testing this combination in a clinical study.


2013 ◽  
Vol 91 (6) ◽  
pp. 391-404 ◽  
Author(s):  
T.P. Yoshino ◽  
U. Bickham ◽  
C.J. Bayne

In vitro cell culture systems from molluscs have significantly contributed to our basic understanding of complex physiological processes occurring within or between tissue-specific cells, yielding information unattainable using intact animal models. In vitro cultures of neuronal cells from gastropods show how simplified cell models can inform our understanding of complex networks in intact organisms. Primary cell cultures from marine and freshwater bivalve and gastropod species are used as biomonitors for environmental contaminants, as models for gene transfer technologies, and for studies of innate immunity and neoplastic disease. Despite efforts to isolate proliferative cell lines from molluscs, the snail Biomphalaria glabrata (Say, 1818) embryonic (Bge) cell line is the only existing cell line originating from any molluscan species. Taking an organ systems approach, this review summarizes efforts to establish molluscan cell cultures and describes the varied applications of primary cell cultures in research. Because of the unique status of the Bge cell line, an account is presented of the establishment of this cell line, and of how these cells have contributed to our understanding of snail host – parasite interactions. Finally, we detail the difficulties commonly encountered in efforts to establish cell lines from molluscs and discuss how these difficulties might be overcome.


2017 ◽  
Vol 28 (3) ◽  
pp. 307-315 ◽  
Author(s):  
Oxana O. Ryabaya ◽  
Andrey N. Inshakov ◽  
Angelina V. Egorova ◽  
Marina A. Emelyanova ◽  
Tatiana V. Nasedkina ◽  
...  

2018 ◽  
Author(s):  
SA Misek ◽  
KM Appleton ◽  
TS Dexheimer ◽  
EM Lisabeth ◽  
RS Lo ◽  
...  

AbstractOver half of cutaneous melanoma tumors have BRAFV600E/Kmutations. Acquired resistance to BRAF inhibitors (BRAFi) remains a major hurdle in attaining durable therapeutic responses. In this study we demonstrate that approximately 50-60% of melanoma cell lines with vemurafenib resistance acquiredin vitroshow activation of RhoA family GTPases. In BRAFi-resistant melanoma cell lines and tumors, activation of RhoA is correlated with decreased expression of melanocyte lineage genes. Using a machine learning approach, we built gene expression-based models to predict drug sensitivity for 265 common anti-cancer compounds. We then projected these signatures onto the collection of TCGA cutaneous melanoma and found that poorly differentiated tumors were predicted to have increased sensitivity to multiple Rho kinase (ROCK) inhibitors. Two transcriptional effectors downstream of Rho, MRTF and YAP1, are activated in the RhoHighBRAFi-resistant cell lines, and resistant cells are more sensitive to inhibition of these transcriptional mechanisms. Taken together, these results support the concept of targeting Rho-regulated gene transcription pathways as a promising therapy approach to restore sensitivity to BRAFi-resistant tumors or as a combination therapy to prevent the onset of drug resistance.


Author(s):  
Inna Divinski ◽  
Inbar Pilzer ◽  
Illana Gozes

2020 ◽  
Vol 21 (17) ◽  
pp. 6183
Author(s):  
Beatrice Polini ◽  
Sara Carpi ◽  
Stefano Doccini ◽  
Valentina Citi ◽  
Alma Martelli ◽  
...  

Background: Remarkable deregulation of several microRNAs (miRNAs) is demonstrated in cutaneous melanoma. hsa-miR-193a-3p is reported to be under-expressed in tissues and in plasma of melanoma patients, but the role of both miR-193a arms in melanoma is not known yet. Methods: After observing the reduced levels of miR-193a arms in plasma exosomes of melanoma patients, the effects of hsa-miR-193a-3p and –5p transfection in cutaneous melanoma cell lines are investigated. Results: In melanoma cell lines A375, 501Mel, and MeWo, the ectopic over-expression of miR-193a arms significantly reduced cell viability as well as the expression of genes involved in proliferation (ERBB2, KRAS, PIK3R3, and MTOR) and apoptosis (MCL1 and NUSAP1). These functional features were accompanied by a significant downregulation of Akt and Erk pathways and a strong increase in the apoptotic process. Since in silico databases revealed TROY, an orphan member of the tumor necrosis receptor family, as a potential direct target of miR-193a-5p, this possibility was investigated using the luciferase assay and excluded by our results. Conclusions: Our results underline a relevant role of miR-193a, both -3p and -5p, as tumor suppressors clarifying the intracellular mechanisms involved and suggesting that their ectopic over-expression could represent a novel treatment for cutaneous melanoma patients.


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