scholarly journals Mechanical Intermittent Compression Affects the Progression Rate of Malignant Melanoma Cells in a Cycle Period-Dependent Manner

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1112
Author(s):  
Takashi Morikura ◽  
Shogo Miyata
Keyword(s):  
Malignant Melanoma ◽  
Mrna Expression ◽  
Melanoma Cells ◽  
Cycle Period ◽  
Progression Rate ◽  
Dependent Manner ◽  
Mechanical Compression ◽  
Dynamic Mechanical ◽  
Intermittent Compression ◽  
Mrna Expression Levels

Static mechanical compression is a biomechanical factor that affects the progression of melanoma cells. However, little is known about how dynamic mechanical compression affects the progression of melanoma cells. In the present study, we show that mechanical intermittent compression affects the progression rate of malignant melanoma cells in a cycle period-dependent manner. Our results suggest that intermittent compression with a cycle of 2 h on/2 h off could suppress the progression rate of melanoma cells by suppressing the elongation of F-actin filaments and mRNA expression levels related to collagen degradation. In contrast, intermittent compression with a cycle of 4 h on/4 h off could promote the progression rate of melanoma cells by promoting cell proliferation and mRNA expression levels related to collagen degradation. Mechanical intermittent compression could therefore affect the progression rate of malignant melanoma cells in a cycle period-dependent manner. Our results contribute to a deeper understanding of the physiological responses of melanoma cells to dynamic mechanical compression.

Imprinting in the schizophrenia candidate gene GABRB2

2011 ◽  
Vol 26 (S2) ◽  
pp. 823-823
Author(s):  
F. Pun ◽  
C. Zhao ◽  
W. Lo ◽  
S. Ng ◽  
S. Tsang ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Mrna Expression ◽  
Association Studies ◽  
Methylation Status ◽  
Dependent Manner ◽  
Expression Levels ◽  
Allele Specific ◽  
Parent Of Origin ◽  
Allele Specific Methylation ◽  
Mrna Expression Levels

Imprinting, characterized by unequal expression of the offspring's genes in a parent-of-origin dependent manner, has been functionally implicated in brain development and in psychiatric disorders. In this study, unambiguous distortion in paternal but not maternal transmission of the disease-associated single-nucleotide polymorphism (SNP) rs6556547 (T/G) clearly indicated the presence of parent-of-origin effect (POE) in the GABAA receptor β2 subunit gene (GABRB2). ‘Flipping’ of allelic mRNA expression in heterozygotes of SNP rs2229944 (C/T) and the observed two-tiered distribution of mRNA expression levels in heterozygotes of the disease-associated SNP rs1816071 (G/A) furnished important support for the occurrence of imprinting at GABRB2. Imprinting in effect introduced heterozygotes from different parents-of-origin endowed with dissimilar mRNA expression capabilities. The deficit of upper-tiered expressions accounted for the lowered mRNA expression levels in the schizophrenic heterozygotes. This pointed to the necessity of differentiating between two kinds of heterozygotes of different parental origins in disease association studies on GABRB2. Bisulfite sequencing revealed hypermethylation in the neighborhood of SNP rs1816071, and methylation differences between controls and schizophrenia patients. Notably, allele-specific methylation was observed at the disease-associated SNPs rs6556547 and rs1816071. These findings raised the possibility that CpG methylation status of these sites could have an impact on the expression of GABRB2 and the risk of schizophrenia. Furthermore, the occurrence of imprinting and allele-specific methylation in the schizophrenia candidate gene GABRB2 was compatible with the epigenetic hypothesis for schizophrenia pathophysiology, thereby calling for the need to explore the role of epigenetic factors in mediating susceptibility to schizophrenia.

scholarly journals Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin

2019 ◽  
Vol 242 (2) ◽  
pp. 13-23 ◽  
Author(s):  
Masaki Nakano ◽  
Mika Ikegame ◽  
Junko Igarashi-Migitaka ◽  
Yusuke Maruyama ◽  
Nobuo Suzuki ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Bone Matrix ◽  
Cathepsin K ◽  
Suppressive Effect ◽  
Melatonin Receptors ◽  
Dependent Manner ◽  
In Ovo ◽  
Expression Levels ◽  
Underlying Mechanisms ◽  
Mrna Expression Levels

Many studies have investigated the actions of melatonin on osteoblasts and osteoclasts. However, the underlying mechanisms, especially regarding osteocyte function, remain largely unknown. Therefore, this study aimed to clarify the underlying mechanisms of melatonin action on bone tissue via osteocyte function. Chick calvariae were employed as a model. In ovo injection of melatonin (5, 50 and 500 µg) dose-dependently decreased the mRNA expression levels of cathepsin K and matrix metalloproteinase 9 (MMP9) in chick calvariae without affecting the expression levels of receptor activator of NF-κB ligand or osteoprotegerin. Surprisingly enough, the expression of calcitonin mRNA in chick calvariae was significantly raised. After 3 days of in vitro treatment of melatonin (10−7 and 10−5 M) on newly hatched chick calvariae, both calcitonin mRNA expression in calvariae and the concentration of calcitonin in cultured medium were augmented in a dose-dependent manner, coincident with the decreased mRNA expression levels of cathepsin K and MMP9. Immunohistochemical analyses revealed expression of melatonin receptors and calcitonin by osteocytes buried in bone matrix. Moreover, the mRNA expression levels of melatonin receptors, calcitonin and sclerostin (a marker of osteocyte), were strongly and positively correlated. In conclusion, we demonstrated the expression of melatonin receptors and calcitonin expression in osteocytes for the first time and suggest a new mechanism underlying the suppressive effect of melatonin on osteoclasts via upregulation of calcitonin secretion by osteocytes.

scholarly journals Biphasic Roles of Clock Genes and Bone Morphogenetic Proteins in Gonadotropin Expression by Mouse Gonadotrope Cells

2021 ◽  
Vol 22 (20) ◽  
pp. 11186
Author(s):  
Yoshiaki Soejima ◽  
Nahoko Iwata ◽  
Yasuhiro Nakano ◽  
Koichiro Yamamoto ◽  
Atsuhito Suyama ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Early Phase ◽  
Clock Genes ◽  
Late Phase ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Gonadotropin Secretion ◽  
Functional Link ◽  
Expression Levels ◽  
Mrna Expression Levels

Roles of Clock genes and the bone morphogenetic protein (BMP) system in the regulation of gonadotropin secretion by gonadotropin-releasing hormone (GnRH) were investigated using mouse gonadotropin LβT2 cells. It was found that luteinizing hormone (LH)β mRNA expression level in LβT2 cells changed gradually over time, with LHβ expression being suppressed in the early phase up to 12 h and then elevated in the late phase 24 h after GnRH stimulation. In addition, the mRNA expression levels of Clock genes, including Bmal1, Clock, Per2, and Cry1, also showed temporal changes mimicking the pattern of LHβ expression in the presence and absence of GnRH. Notably, the expression levels of Bmal1 and Clock showed strong positive correlations with LHβ mRNA expression levels. Moreover, a functional link of the ERK signaling of mitogen-activated protein kinases (MAPKs) in the suppression of LHβ mRNA expression, as well as Bmal1 and Clock mRNA expression by GnRH at the early phase, was revealed. Inhibition of Bmal1 and Clock expression using siRNA was involved in the reduction in LHβ mRNA levels in the late phase 24 h after GnRH stimulation. Furthermore, in the presence of BMP-6 and -7, late-phase Bmal1 and LHβ mRNA expression after GnRH stimulation was significantly attenuated. Collectively, the results indicated that LH expression in gonadotrope cells exhibits Bmal1/Clock-dependent fluctuations under the influence of GnRH and that the fluctuations are regulated by ERK and BMPs in the early and late stages, respectively, in a phase-dependent manner after GnRH stimulation.

scholarly journals Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells

2017 ◽  
Vol 18 (3) ◽  
pp. 532 ◽  
Author(s):  
Eun-Ji Park ◽  
Yoon-Mi Lee ◽  
Taek-In Oh ◽  
Byeong Kim ◽  
Beong-Ou Lim ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Cell Motility ◽  
Mrna Expression ◽  
Melanoma Cells

Inhibition of Melanogenesis in Murine B16/F10 Melanoma Cells by Ligusticum sinensis Oliv.

2006 ◽  
Vol 34 (03) ◽  
pp. 523-533 ◽  
Author(s):  
Ching-Yuan Wu ◽  
Jong-Hwei S. Pang ◽  
Sheng-Teng Huang
Keyword(s):  
Mrna Expression ◽  
Oxidase Activity ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Melanoma Cells ◽  
Dependent Manner ◽  
Mushroom Tyrosinase ◽  
Tyrosinase Gene ◽  
Direct Inhibitory Effect ◽  
Dopa Oxidase

Ligusticum sinensis Oliv. (LSO) is an herbal drug commonly used as a topical treatment of epidermal hyperdepigmentation in Chinese medicine. However, the mechanism underlying the depigmentation by LSO is still unclear. The purpose of this study was to investigate the effects of LSO on the process of melanogenesis and its possible underlying mechanism. Suppressed DOPA oxidase activity of mushroom tyrosinase was first noted when incubated with aqueous extracts of LSO, demonstrating the direct inhibitory effect of LSO on mushroom tyrosinase. Further experiments were carried out in murine B16/F10 melanoma cells and the effects of LSO extract on melanin formation, tyrosinase activity and tyrosinase gene expression were tested. Under conditions without affecting the viability of murine B16/F10 melanoma cells, LSO extract significantly reduced the cellular melanin content in a dose-dependent manner. The DOPA oxidase activity of tyrosinase in B16/F10 cells was dose-dependently inhibited by LSO treatment, possibly mediated by the suppressed tyrosinase mRNA expression in LSO-treated B16/F10 cells. In conclusion, the inhibitory effect of LSO on melanogenesis is likely associated with decreased DOPA oxidase activity of tyrosinase that is most likely the result of the down-regulation of tyrosinase mRNA expression.

scholarly journals The effect of micro-sized titanium dioxide on WM-266-4 metastatic melanoma cell line

2019 ◽  
Vol 19 (1) ◽  
pp. 60-66
Author(s):  
Tanja Prunk Zdravković ◽  
Bogdan Zdravković ◽  
Mojca Lunder ◽  
Polonca Ferk
Keyword(s):  
Titanium Dioxide ◽  
Mrna Expression ◽  
Metastatic Melanoma ◽  
Cell Line ◽  
Metabolic Activity ◽  
Melanoma Cell Line ◽  
Melanoma Cells ◽  
Time Dependent ◽  
Dependent Manner ◽  
Metastatic Melanoma Cell

Titanium dioxide (TiO2) is widely used as an inorganic UV-filter in cosmetic products; however, it has been classified as possibly carcinogenic to humans. While numerous studies demonstrated cytotoxic and genotoxic effects of nano-sized TiO2 in different cell lines, including human skin cells, studies investigating the effects of micro-TiO2 on human keratinocytes and melanocytes, in healthy and cancer cells, are scarce. Adenosine triphosphate (ATP) binding cassette subfamily B member 5 (ABCB5) is a plasma membrane protein known for its role in the tumorigenicity, progression, and recurrence of melanoma. Here, we investigated the effect of micro-TiO2 (average particle size ≤5 µm) on the metabolic activity, cytotoxicity and ABCB5 mRNA expression in metastatic melanoma cells. Metastatic melanoma cell line WM-266-4 was treated with different concentrations of micro-TiO2 for different incubation times to obtain dose- and time-dependent responses. Untreated WM-266-4 cells, cultured under the same conditions, were used as control. The cell metabolic activity was determined by MTT assay. Cytotoxicity of micro-TiO2 was analyzed by lactate dehydrogenase (LDH) cytotoxicity assay. The ABCB5 mRNA expression in melanoma cells was analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR). After 120 hours of exposure to micro-TiO2 the metabolic activity of melanoma cells decreased, especially at the two highest micro-TiO2 concentrations. Comparably, the cytotoxicity of micro-TiO2 on melanoma cells increased after 48 and 120 hours of exposure, in a time-dependent manner. The ABCB5 mRNA expression in micro-TiO2-treated melanoma cells also decreased significantly after 24 and 48 hours, in a time-dependent manner. Overall, our results suggest inhibitory effects of micro-TiO2 on the metabolic activity and ABCB5 mRNA expression in metastatic melanoma cells, indicating its potential use as an anticancer agent.

Ferruginol induced apoptosis on SK-Mel-28 human malignant melanoma cells mediated through P-p38 and NF-κB

2018 ◽  
Vol 38 (2) ◽  
pp. 227-238 ◽  
Author(s):  
Y Jia ◽  
C Wu ◽  
B Zhang ◽  
Y Zhang ◽  
J Li
Keyword(s):  
Dna Damage ◽  
Malignant Melanoma ◽  
Caspase 3 ◽  
Nuclear Translocation ◽  
Annexin V ◽  
Melanoma Cells ◽  
Prolonged Treatment ◽  
Dependent Manner ◽  
Human Malignant Melanoma ◽  
Induced Apoptosis

In the present investigation, the antitumor effect of ferruginol (FGL) in SK-Mel-28 human malignant melanoma cells was studied. To investigate the cytotoxic property of FGL, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used. Results revealed that prolonged treatment duration decreases the IC25, IC50, and IC75 concentrations of FGL. The cytotoxicity was further confirmed by lactate dehydrogenase assay. As evident from comet assay, FGL induces DNA damage in a dose-dependent manner. Annexin V and 7-ADD assays showed that FGL-induced DNA damage triggers apoptosis-mediated cell death as confirmed by caspase-3 activity assay. As seen through Western blotting, FGL increases phosphorylation of p38 and nuclear translocation of NF-κB. Further, it was observed that p38 phosphorylation is responsible for NF-κB translocation to the nucleus. Further, inhibition of p38 phosphorylation and translocation of NF-κB decrease caspase-3 activity. The above finding confirms that caspase-3 activation is mediated through P-p38 and nuclear translocation of NF-κB. The present findings indicate that FGL significantly suppresses the proliferation of SK-Mel-28 cells in a dose- and time-dependent manner through induction of apoptosis. Furthermore, FGL executes apoptosis through phosphorylation of key protein such as p38 and translocation of NF-κB into the nucleus.

scholarly journals Blocking of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells

2020 ◽  
Author(s):  
Young-shin Lee ◽  
Woong Heo ◽  
Ho-Jung Choi ◽  
Hae-Ryung Cho ◽  
Ji Ho Nam ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Ionizing Radiation ◽  
Immune Responses ◽  
Nk Cells ◽  
Cancer Cells ◽  
Melanoma Cells ◽  
Cell Mediated Immunity ◽  
Dependent Manner ◽  
Programmed Death ◽  
Programmed Death 1

Abstract Background Since ionizing radiation has showed the dramatic effect to kill the cancer cells by direct DNA damage as well as triggering anti-cancer immune responses through release of various tumor antigens and induction of NK activating molecules, it has been used for long time to treat many cancer patients including patients with melanoma. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system. One of the suggested ways is induction of a ligand for programmed death-1 (PD-L1) after radiotherapy in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity in T cells. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1/2 in malignant melanoma cells and the receptor, PD-1, in NK-92 cells. Results Surface PD-L1/2 levels on melanoma cells were increased by ionizing radiation in a dose-dependent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1/2 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1/2+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene to inhibit PD-1/PD-L1 axis, they reversed the activity of the suppressed NK cells. Conclusions Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.

scholarly journals Effect of Mechanical Compression on Invasion Process of Malignant Melanoma Using In Vitro Three-Dimensional Cell Culture Device

Micromachines ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 666 ◽  
Author(s):  
Morikura ◽  
Miyata
Keyword(s):  
Cell Culture ◽  
Malignant Melanoma ◽  
Three Dimensional ◽  
Melanoma Cells ◽  
Invasion Process ◽  
Mechanical Compression ◽  
Invasion Mechanisms ◽  
Significant Difference ◽  
Dimensional Cell

Malignant melanoma in the plantar surface of the foot is subjected to various mechanical stimuli generated by daily human activity such as walking. Some studies have reported that mechanical compression affects the development and progression of melanoma. However, little is known about how mechanical compression affects the behavior of malignant melanoma cells in a physiological condition due to the complexity of the invasion mechanisms. In this study, we developed an in vitro three-dimensional cell culture device using microporous membrane in order to evaluate the effects of mechanical compression on the invasion process of malignant melanoma. Our results suggest that the invasion of melanoma cells under the compressive stress for 8 h of culture was promoted with the elongation of F-actin filaments compared to control groups, whereas there was no significant difference between both groups at 32 h of culture, with increasing cell death associated with promoting melanin synthesis. The results of this study contribute to the elucidation of the invasion mechanisms of malignant melanoma caused by mechanical stimulation.

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