scholarly journals Modulation of cell growth and cisplatin sensitivity by membrane γ-glutamyltransferase in melanoma cells

2006 ◽  
Vol 42 (15) ◽  
pp. 2623-2630 ◽  
Author(s):  
Maria Franzini ◽  
Alessandro Corti ◽  
Evelina Lorenzini ◽  
Aldo Paolicchi ◽  
Alfonso Pompella ◽  
...  
Keyword(s):  
Cell Growth ◽  
Melanoma Cells ◽  
Cisplatin Sensitivity

scholarly journals miR-548b-3p Regulates Proliferation, Apoptosis, and Mitochondrial Function by Targeting CIP2A in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Lin Lin ◽  
Yong Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Growth ◽  
Mitochondrial Function ◽  
Luciferase Reporter ◽  
Target List ◽  
Downstream Target ◽  
Normal Tissues ◽  
Cisplatin Sensitivity ◽  
Cell Cycle Transition

The roles of miR-548b-3p in the progression of hepatocellular carcinoma (HCC) remain undiscovered. This study aims to explore the roles and mechanisms of miR-548b-3p in HCC. Using TCGA database, we found that miR-548b-3p expression was lower in HCC compared to the normal tissues, which was further confirmed by RT-qPCR of 20 cases of surgically resected HCC and corresponding normal tissues. miR-548b-3p mimic and inhibitor were transfected into Huh7 and SK-Hep-1 cells, respectively. MTT, colony formation, and cell cycle assays showed that miR-548b-3p mimic suppressed cell growth and G1/S cell cycle transition. In contrast, miR-548b-3p inhibitor facilitated cell growth and cell cycle transition. miR-548b-3p mimic also increased cisplatin sensitivity by upregulating apoptosis rate. JC-1 staining showed that miR-548b-3p mimic downregulated mitochondrial membrane potential, while miR-548b-3p inhibitor showed the opposite effects in SK-Hep-1 cells. Using prediction software, we found that CIP2A was on the target list of miR-548b-3p. miR-548b-3p mimic downregulated CIP2A and its downstream target protein c-Myc. Luciferase reporter assay demonstrated that CIP2A was as a direct target of miR-548b-3p. CIP2A depletion partly reduced the effect of miR-548b-3p mimic/inhibitor on c-Myc. CIP2A depletion also reduced the effect of miR-548b-3p mimic/inhibitor on proliferation. In conclusion, our data demonstrated that miR-548b-3p was downregulated in HCC. miR-548b-3p regulates proliferation, apoptosis and mitochondrial function by targeting CIP2A in HCC.

scholarly journals Cinobufagin Suppresses Melanoma Cell Growth by Inhibiting LEF1

2020 ◽  
Vol 21 (18) ◽  
pp. 6706
Author(s):  
Geon-Hee Kim ◽  
Xue-Quan Fang ◽  
Woo-Jin Lim ◽  
Jooho Park ◽  
Tae-Bong Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Melanoma Cell ◽  
Transcriptional Activity ◽  
Melanoma Cells ◽  
Lung Cancer Cells ◽  
Luciferase Assay ◽  
Dependent Manner

Constitutive activation of the β-catenin dependent canonical Wnt signaling pathway, which enhances tumor growth and progression in multiple types of cancer, is commonly observed in melanoma. LEF1 activates β-catenin/TCF4 transcriptional activity, promoting tumor growth and progression. Although several reports have shown that LEF1 is highly expressed in melanoma, the functional role of LEF1 in melanoma growth is not fully understood. While A375, A2058, and G361 melanoma cells exhibit abnormally high LEF1 expression, lung cancer cells express lower LEF1 levels. A luciferase assay-based high throughput screening (HTS) with a natural compound library showed that cinobufagin suppressed β-catenin/TCF4 transcriptional activity by inhibiting LEF1 expression. Cinobufagin decreases LEF1 expression in a dose-dependent manner and Wnt/β-catenin target genes such as Axin-2, cyclin D1, and c-Myc in melanoma cell lines. Cinobufagin sensitively attenuates cell viability and induces apoptosis in LEF1 expressing melanoma cells compared to LEF1-low expressing lung cancer cells. In addition, ectopic LEF1 expression is sufficient to attenuate cinobufagin-induced apoptosis and cell growth retardation in melanoma cells. Thus, we suggest that cinobufagin is a potential anti-melanoma drug that suppresses tumor-promoting Wnt/β-catenin signaling via LEF1 inhibition.

Decitabine, independent of apoptosis, exerts its cytotoxic effects on cell growth in melanoma cells

2011 ◽  
Vol 32 (3) ◽  
pp. 423-429 ◽  
Author(s):  
Qian-Ying Liu ◽  
Da-Wei Chen ◽  
Li-Ping Xie ◽  
Rong-Qing Zhang ◽  
Hong-Zhong Wang
Keyword(s):  
Cell Growth ◽  
Melanoma Cells ◽  
Cytotoxic Effects

scholarly journals ROS production induced by BRAF inhibitor treatment rewires metabolic processes affecting cell growth of melanoma cells

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Giulia Cesi ◽  
Geoffroy Walbrecq ◽  
Andreas Zimmer ◽  
Stephanie Kreis ◽  
Claude Haan
Keyword(s):  
Cell Growth ◽  
Braf Inhibitor ◽  
Melanoma Cells ◽  
Ros Production ◽  
Metabolic Processes ◽  
Inhibitor Treatment

scholarly journals CCN4 shifts melanoma cells from a fragile proliferative state to a resilient metastatic state

2018 ◽  
Author(s):  
Wentao Deng ◽  
Audry Fernandez ◽  
Sarah L. McLaughlin ◽  
David J. Klinke
Keyword(s):  
Cell Growth ◽  
Cell Survival ◽  
Intracellular Signaling ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Culture Conditions ◽  
Matricellular Protein ◽  
Melanoma Progression

ABSTRACTWhile deregulated intracellular signaling initiates melanoma, intercellular crosstalk within the tumor microenvironment, often coordinated by soluble factors, is essential for melanoma progression and metastasis. One such secreted matricellular protein, cellular communication network factor 4 (CCN4), stimulates metastasis in other malignancies. Here, we report that CCN4 expression is associated progressively with reduced overall survival in patients with primary melanomas. To reveal the roles of CCN4 in melanoma progression, we used mouse melanoma models and knocked outCcn4using a homology-directed repair CRISPR/CAS9 system to generate pools ofCcn4-knockout cells.In vitroassays supported previous findings using clones generated using a double nickase-based CRISPR/CAS9 system that CCN4 promoted an epithelial – mesenchymal-like transition in melanoma cells and stimulated invasion and metastasis. We also found that, whileCcn4knockout enhanced cell growth in optimal 2D culture conditions, the knockout suppressed certain cell survival signaling pathways and rendered cells less resistant to stress conditions. Tumor cell growth assays at sub-optimal conditionsin vitro, quantitative analysis of tumor growth assaysin vivo,and transcriptomics analysis of human melanoma cell lines suggested that CCN4 repressed cell growth and simultaneously enhanced cell survival. The collective role of CCN4 suggests a potential therapeutic target for limiting metastatic invasion in melanoma and a biomarker for metastatic potential.

Temozolomide combined with the PI3K inhibitor LY294002 or the mTOR inhibitor rapamycin inhibits melanoma cell growth, survival and invasion

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8559-8559 ◽  
Author(s):  
F. E. Meier ◽  
K. Lasithiotakis ◽  
B. Schittek ◽  
T. Sinnberg ◽  
C. Garbe
Keyword(s):  
Cell Growth ◽  
Metastatic Melanoma ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Mtor Inhibitor ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Pi3k Inhibitor ◽  
Mapk Signaling Pathways

8559 Background: Potential therapeutic targets in the treatment of metastatic melanoma have emerged, to which pharmacological inhibitors have been designed, which may enhance tumor chemosensitivity. In melanoma, dacarbazine is considered to be the most effective agent although total responses do not exceed 20% The clinical activity of temozolomide is similar to that of dacarbazine, but temozolomide has the advantages of being absorbed orally and of crossing the blood-brain barrier. Many clinical trials of targeted therapy and chemotherapy combinations lack rigorous preclinical evaluation and may neglect relevant mechanistic interactions. The PI3K-AKT-mTOR (AKT) and RAS-RAF- MEK-ERK (MAPK) signaling pathways are constitutively activated in melanoma, and appear to play a role in chemoresistance. Methods: In this study, a panel of pharmacological inhibitors was utilized in order to block the AKT and MAPK signaling pathways at different levels (AKT: PI3K, mTOR; MAPK: RAF, MEK) in 5 human metastatic melanoma cell lines. The effects on chemosensitivity to temozolomide and cisplatin was then investigated. Results: The effects of most inhibitors on chemosensitivity varied significantly between the different cell lines. However, LY294002, a PI3K inhibitor and rapamycin, an mTOR inhibitor, consistently enhanced chemosensitivity. Treatment of melanoma cells with temozolomide or cisplatin combined with LY294002 or rapamycin had a strong effect on melanoma cell growth and survival. Invasive melanoma growth in organotypic cultures of human skin was suppressed completely. The most pronounced potentiation of efficacy was seen with temozolomide in combination with rapamycin. Conclusions: These data suggest that LY294002 and rapamycin can render melanoma cells susceptible to apoptosis, induced by chemotherapeutic agents such as temozolomide and cisplatin. Since both temozolomide and rapamycin are used clinically, the combination of temozolomide with rapamycin might potentially be utilized as an approach in melanoma treatment. This combination merits clinical investigation. No significant financial relationships to disclose.

scholarly journals Subcutaneous Adipocytes Promote Melanoma Cell Growth by Activating the Akt Signaling Pathway

2014 ◽  
Vol 289 (44) ◽  
pp. 30525-30537 ◽  
Author(s):  
Hiu Yee Kwan ◽  
Xiuqiong Fu ◽  
Bin Liu ◽  
Xiaojuan Chao ◽  
Chi Leung Chan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Growth ◽  
Palmitic Acid ◽  
Melanoma Cell ◽  
Underlying Mechanism ◽  
Melanoma Cells ◽  
Cell Cycle Distribution ◽  
Tensin Homolog ◽  
B16f10 Cells ◽  
Isolated Adipocytes

Tumorigenesis involves constant communication between tumor cells and neighboring normal cells such as adipocytes. The canonical function of adipocytes is to store triglyceride and release fatty acids for other tissues. This study was aimed to find out if adipocytes promoted melanoma cell growth and to investigate the underlying mechanism. Here we isolated adipocytes from inguinal adipose tissue in mice and co-cultured with melanoma cells. We found that the co-cultured melanoma had higher lipid accumulation compared with mono-cultured melanoma. In addition, fluorescently labeled fatty acid BODIPY® FLC16 signal was detected in melanoma co-cultured with the adipocytes that had been loaded with the fluorescent dye, suggesting that the adipocytes provide fatty acids to melanoma cells. Compared with mono-cultured melanoma, co-cultured melanoma cells had a higher proliferation and phospho-Akt (Ser-473 and Thr-450) expression. Overexpression of Akt mutants in melanoma cells reduced the co-culture-enhanced proliferation. A lipidomic study showed that the co-cultured melanoma had an elevated palmitic acid level. Interestingly, we found that palmitic acid stimulated melanoma cell proliferation, changed the cell cycle distribution, and increased phospho-Akt (Ser-473 and Thr-450) and PI3K but not phospho-PTEN (phosphophosphatase and tensin homolog) expressions. More importantly, the palmitic acid-stimulated proliferation was further enhanced in the Akt-overexpressed melanoma cells and was reduced by LY294002 or knockdown of endogenous Akt or overexpression of Akt mutants. We also found that palmitic acid-pretreated B16F10 cells were grown to a significantly larger tumor in mice compared with control cells. Taken together, we suggest that adipocytes may serve as an exogenous source of palmitic acid that promotes melanoma cell growth by activating Akt.

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