scholarly journals H2AFZ: A Novel Prognostic Marker in Canine Melanoma and a Predictive Marker for Resistance to CDK4/6 Inhibitor Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Laura Bongiovanni ◽  
Anneloes Andriessen ◽  
Serenella Silvestri ◽  
Ilaria Porcellato ◽  
Chiara Brachelente ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Target Gene ◽  
Predictive Marker ◽  
Expression Levels ◽  
Anti Cancer ◽  
Canine Melanoma ◽  
Melanoma Cell Lines

Uncontrolled proliferation is a key feature of tumor progression and malignancy. This suggests that cell-cycle related factors could be exploited as cancer biomarkers and that pathways specifically involved in the cell cycle, such as the Rb-E2F pathway, could be targeted as an effective anti-tumor therapy. We investigated 34 formalin-fixed paraffin-embedded (FFPE) tissue samples of canine cutaneous melanocytoma, cutaneous melanoma, and oral melanoma. Corresponding clinical follow-up data were used to determine the prognostic value of the mRNA expression levels of several cell cycle regulated E2F target genes (E2F1, DHFR, CDC6, ATAD2, MCM2, H2AFZ, GINS2, and survivin/BIRC5). Moreover, using four canine melanoma cell lines, we explored the possibility of blocking the Rb-E2F pathway by using a CDK4/6 inhibitor (Palbociclib) as a potential anti-cancer therapy. We investigated the expression levels of the same E2F target gene transcripts before and after treatment to determine the potential utility of these molecules as predictive markers. The E2F target gene H2AFZ was expressed in 91.43% of the primary tumors and H2AFZ expression was significantly higher in cases with unfavorable clinical outcome. Among the other tested genes, survivin/BIRC5 showed as well-promising results as a prognostic marker in canine melanoma. Three of the four tested melanoma cell lines were sensitive to the CDK4/6 inhibitor. The resistant cell line displayed higher expression levels of H2AFZ before treatment compared to the CDK4/6 inhibitor-sensitive cell lines. The present results suggest that CDK4/6 inhibitors could potentially be used as a new anti-cancer treatment for canine melanoma and that H2AFZ could serve as a prognostic and predictive marker for patient selection.

scholarly journals Effect of Natural and Synthetic Retinoids on the Proliferation and Differentiation of Three Canine Melanoma Cell Lines

2002 ◽  
Vol 64 (2) ◽  
pp. 169-172 ◽  
Author(s):  
Emi OHASHI ◽  
Kaori INOUE ◽  
Hiroyuki KAGECHIKA ◽  
Sung-Hyeok HONG ◽  
Takayuki NAKAGAWA ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Proliferation And Differentiation ◽  
Canine Melanoma ◽  
Melanoma Cell Lines ◽  
Natural And Synthetic

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 Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines

2014 ◽  
Vol 10 (1) ◽  
pp. 160 ◽  
Author(s):  
Megan N Breit ◽  
William C Kisseberth ◽  
Misty D Bear ◽  
Yosef Landesman ◽  
Trinayan Kashyap ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
Nuclear Export ◽  
Selective Inhibitor ◽  
The Novel ◽  
Biologic Activity ◽  
Orally Bioavailable ◽  
Canine Melanoma ◽  
Melanoma Cell Lines

scholarly journals 6-Bromoindirubin-3′oxime (BIO) decreases proliferation and migration of canine melanoma cell lines

2015 ◽  
Vol 205 (2) ◽  
pp. 305-312 ◽  
Author(s):  
Esther Chon ◽  
Brandi Flanagan ◽  
Lucas Campos de Sá Rodrigues ◽  
Caroline Piskun ◽  
Timothy J. Stein
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
And Migration ◽  
Canine Melanoma ◽  
Melanoma Cell Lines ◽  
Proliferation And Migration

Anticancer effects of high-dose ascorbate on canine melanoma cell lines

2018 ◽  
Vol 16 (4) ◽  
pp. 616-621 ◽  
Author(s):  
Hyeri Shin ◽  
Aryung Nam ◽  
Kun-Ho Song ◽  
Kupil Lee ◽  
Robert B. Rebhun ◽  
...  
Keyword(s):  
Cell Lines ◽  
Melanoma Cell ◽  
High Dose ◽  
Anticancer Effects ◽  
Canine Melanoma ◽  
Melanoma Cell Lines

Effect of microRNA-206 on G1 arrest by inhibition of CDK4, cyclin C, and cyclin D in melanoma cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20047-e20047 ◽  
Author(s):  
Robert W Georgantas ◽  
Katie Streicher ◽  
Xiaobing Luo ◽  
Wei Zhu ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Normal Skin ◽  
G1 Arrest ◽  
Mrna Targets ◽  
Cyclin C ◽  
Skin Biopsies ◽  
Melanoma Cell Lines

e20047 Background: MiR-206 has been implicated in a large number of cancers. However, its role in tumor biology is unknown and its biological function has yet to be fully characterized. To examine the role of miR-206 in cancer, we examined the expression of miR-206 in melanoma and identified potential target transcriptss that could be important for the progression of this disease. Methods: Using quantitative RT-PCR we compared expression of 364 microRNAs in melanoma skin biopsies skin from normal donors, melanoma cell lines, and normal melanocytes. The effects of miR-206 on cell growth, apoptosis, and cellular migration/invasion were determined using in vitro assays comparing melanoma cell lines to normal melanocytes. Putative mRNA targets of miR-206 were bioinfomatically identified, and empirically tested by luciferase-3’UTR reporter assays. The effect of miR-206 on the cell cycle of melanoma cells was assayed by flow cytometry. Results: Expression profiling of microRNAs in melanoma lesional skin biopsies compared to normal donor skin biopsies revealed numerous differentially regulated miRs. One such microRNA, miR-206, was significantly highly down-regulated in melanoma biopsies (-75.4-fold, p=1.7x10-4) compared to normal skin and normal melanocytes. Functional analysis showed that miR-206 substantially reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatic analysis identified the cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate mRNA targets of miR-206. Luciferase reporter gene assays revealed that miR-206 inhibits translation of CDK4, Cyclin D1, and Cyclin C. Consistent with this inhibition of CDK4 and Cyclin D1, miR-206 transfection induced robust G1 arrest in multiple melanoma cell lines. Conclusions: MiR-206 expression was decreased in melanoma tissue and cell lines compared to normal skin and melanocytes, respectively. Inhibition of Cyclin C, Cyclin D1 and CDK4 by miR-206 highlights its role in regulating cell cycle progression, a key aspect of melanoma progression. These observations support miR-206 as a potential tumor suppressor in melanoma, and possibly other cancers.

Melatonin inhibits human melanoma cells proliferation and invasion via cell cycle arrest and cytoskeleton remodeling

2020 ◽  
Vol 3 (2) ◽  
pp. 194-209 ◽  
Author(s):  
Ana Carolina Ramos Moreno ◽  
Renata de Freitas Saito ◽  
Manoela Tiago ◽  
Renato Ramos Massaro ◽  
Roberta Liberato Pagni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Cell Swelling ◽  
Cycle Arrest ◽  
Cytoskeleton Remodeling ◽  
Melanoma Cell Lines

Among skin cancers, melanoma has the highest mortality rate. The heterogeneous genetic melanoma background leads to a tumor-propagating capacity particularly important in maintaining therapeutic resistance, and tumor recurrence. The identification of efficient molecules able to control melanoma progress represents an important opportunity for new therapeutic strategies, particularly in combination with the current standard-of-care treatments. In this context, several studies have reported the antitumor effects of melatonin against different types of cancer, including melanoma. Here, we describe the underlying mechanisms associated with melatonin’s activity in human melanoma cell lines, focusing on cell cycle and cytoskeleton remodeling. Interestingly, while melatonin induced melanocyte DNA replication, melanoma cells exhibited cell cycle arrest in the G1-phase. This phenomenon was associated with cyclin-D1 downregulation or p21 overexpression. The efficacy of melatonin on melanoma cells survival and proliferation was detected using the clonogenic assay, with a decrease in both the number and size of colonies. Additionally, melatonin induced a dramatic cytoskeleton remodeling in all melanoma cell lines, leading to a star-like morphology or cell swelling. The role of melatonin on melanoma cytoskeleton was associated with the actin disruption, with thinning and/or broken actin fibers, and weak and/or loss of paxillin along stress fibers. These data support the observed findings that melatonin impairs melanoma invasion in skin reconstructed models. Together, our results suggest that melatonin could be used to control melanoma growth and support basic and clinical studies on melatonin as a promising immunometabolic adjuvant for melanoma therapy.

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