scholarly journals Inhibitory Effects of Trehalose on Malignant Melanoma Cell Growth: Implications for a Novel Topical Anticancer Agent on the Ocular Surface

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Takashi Kudo ◽  
Kimio Takeuchi ◽  
Yu-ichi Ebina ◽  
Mitsuru Nakazawa
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Growth ◽  
Malignant Melanoma ◽  
Melanoma Cell ◽  
Ocular Surface ◽  
Melanoma Cells ◽  
Apoptotic Cells ◽  
Inhibitory Effects ◽  
Malignant Melanoma Cell

Purpose. To investigate the inhibitory effects of trehalose on malignant melanoma cell growth. Methods. We cultured human malignant melanoma cells in a medium containing trehalose (control/2.5%/5.0%/7.5%/10.0%) and used the MTT assay to evaluate the growth activities. Subsequently, trehalose was topically instilled on subconjunctivally inoculated melanoma cells in F334/NJcl-rmu/rmu rats, followed by a histopathological evaluation of tumor growth. Using flow cytometry, we compared the distribution of the cell cycle, rate of apoptotic cells, and intracellular factors related to the cell cycle in cultured melanoma cells after trehalose treatment. Results. The MTT study showed that proliferation of melanoma cells was significantly inhibited by ≧ 5% of trehalose concentrations in the culture media. Subconjunctivally inoculated melanoma cell masses were significantly smaller in eyes administered trehalose as compared to controls. Flow cytometry analyses demonstrated that the trehalose groups had increased rates of G2/M phase cells and apoptotic cells in the cell culture. These cells also exhibited increased expressions of cell-cycle inhibitory factors. Conclusions. The current results show trehalose inhibits malignant melanoma cell growth by inducing G2/M cell cycle arrest and apoptosis, suggesting trehalose as a potential candidate for a topical agent to inhibit proliferation of malignant tumor cells of the ocular surface.

scholarly journals Anti-oncogenic MicroRNA-203 Induces Senescence by Targeting E2F3 Protein in Human Melanoma Cells

2012 ◽  
Vol 287 (15) ◽  
pp. 11769-11777 ◽  
Author(s):  
Shunsuke Noguchi ◽  
Takashi Mori ◽  
Yusami Otsuka ◽  
Nami Yamada ◽  
Yuki Yasui ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Malignant Melanoma ◽  
Cell Cycle Arrest ◽  
Ectopic Expression ◽  
Melanoma Cells ◽  
Microrna Target ◽  
Human Malignant Melanoma ◽  
Cycle Arrest ◽  
Tissue Specimens

MicroRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of their complementary mRNA. We recently reported that miR-203 is down-regulated, and its exogenous expression inhibits cell growth in canine oral malignant melanoma tissue specimens as well as in canine and human malignant melanoma cells. A microRNA target database predicted E2F3 and ZBP-89 as putative targets of microRNA-203 (miR-203). The expression levels of E2F3a, E2F3b, and ZBP-89 were markedly up-regulated in human malignant melanoma Mewo cells compared with those in human epidermal melanocytes. miR-203 significantly suppressed the luciferase activity of reporter plasmids containing the 3′-UTR sequence of either E2F3 or ZBP-89 complementary to miR-203. The ectopic expression of miR-203 in melanoma cells reduced the levels of E2F3a, E2F3b, and ZBP-89 protein expression. At the same time, miR-203 induced cell cycle arrest and senescence phenotypes, such as elevated expression of hypophosphorylated retinoblastoma and other markers for senescence. Silencing of E2F3, but not of ZBP-89, inhibited cell growth and induced cell cycle arrest and senescence. These results demonstrate a novel role for miR-203 as a tumor suppressor acting by inducing senescence in melanoma cells.

scholarly journals E3 ubiquitin ligase PARK2, an inhibitor of melanoma cell growth, is repressed by the oncogenic ERK1/2-ELK1 transcriptional axis

2020 ◽  
Vol 295 (47) ◽  
pp. 16058-16071
Author(s):  
Valentina Montagnani ◽  
Luisa Maresca ◽  
Alessandro Apollo ◽  
Sara Pepe ◽  
Ryan M. Carr ◽  
...  
Keyword(s):  
Cell Growth ◽  
Malignant Melanoma ◽  
Melanoma Cell ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Braf V600e ◽  
Promising Therapeutic Approach ◽  
Melanoma Growth

Malignant melanoma, the most aggressive form of skin cancer, is characterized by high prevalence of BRAF/NRAS mutations and hyperactivation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), mitogen-activated protein kinases (MAPK), leading to uncontrolled melanoma growth. Efficacy of current targeted therapies against mutant BRAF or MEK1/2 have been hindered by existence of innate or development of acquired resistance. Therefore, a better understanding of the mechanisms controlled by MAPK pathway driving melanogenesis will help develop new treatment approaches targeting this oncogenic cascade. Here, we identify E3 ubiquitin ligase PARK2 as a direct target of ELK1, a known transcriptional effector of MAPK signaling in melanoma cells. We show that pharmacological inhibition of BRAF-V600E or ERK1/2 in melanoma cells increases PARK2 expression. PARK2 overexpression reduces melanoma cell growth in vitro and in vivo and induces apoptosis. Conversely, its genetic silencing increases melanoma cell proliferation and reduces cell death. Further, we demonstrate that ELK1 is required by the BRAF-ERK1/2 pathway to repress PARK2 expression and promoter activity in melanoma cells. Clinically, PARK2 is highly expressed in WT BRAF and NRAS melanomas, but it is expressed at low levels in melanomas carrying BRAF/NRAS mutations. Overall, our data provide new insights into the tumor suppressive role of PARK2 in malignant melanoma and uncover a novel mechanism for the negative regulation of PARK2 via the ERK1/2-ELK1 axis. These findings suggest that reactivation of PARK2 may be a promising therapeutic approach to counteract melanoma growth.

scholarly journals 050 Malignant melanoma cell growth is prevented in the systemic inflammatory environment

2020 ◽  
Vol 140 (7) ◽  
pp. S5
Author(s):  
Y. Matsushima ◽  
K. Mizutani ◽  
S. Iida ◽  
A. Umaoka ◽  
K. Okada ◽  
...  
Keyword(s):  
Cell Growth ◽  
Malignant Melanoma ◽  
Melanoma Cell ◽  
Malignant Melanoma Cell

scholarly journals Cell-cycle-controlled radiation therapy was effective for treating a murine malignant melanoma cell line in vitro and in vivo

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Keisuke Otani ◽  
Yoko Naito ◽  
Yukako Sakaguchi ◽  
Yuji Seo ◽  
Yutaka Takahashi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Radiation Therapy ◽  
Malignant Melanoma ◽  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Malignant Melanoma Cell
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