scholarly journals Ketoprofen Combined with UVA Irradiation Exerts Higher Selectivity in the Mode of Action against Melanotic Melanoma Cells than against Normal Human Melanocytes

2021 ◽  
Vol 22 (21) ◽  
pp. 11966
Author(s):  
Klaudia Banach ◽  
Justyna Kowalska ◽  
Zuzanna Rzepka ◽  
Artur Beberok ◽  
Jakub Rok ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Melanoma Cells ◽  
Cell Cycle Distribution ◽  
Surgical Removal ◽  
Membrane Breakdown ◽  
Uva Irradiation ◽  
Human Melanocytes ◽  
Apoptotic Effect ◽  
Cell Cycle Deregulation ◽  
Induced Apoptosis

Malignant melanoma is responsible for the majority of skin cancer-related deaths. The methods of cancer treatment include surgical removal, chemotherapy, immunotherapy, and targeted therapy. However, neither of these methods gives satisfactory results. Therefore, the development of new anticancer therapeutic strategies is very important and may extend the life span of people suffering from melanoma. The aim of this study was to examine the effect of ketoprofen (KTP) and UVA radiation (UVAR) therapy on cell proliferation, apoptosis, and cell cycle distribution in both melanotic melanoma cells (COLO829) and human melanocytes (HEMn-DP) in relation to its supportive effect in the treatment of melanoma. The therapy combining the use of pre-incubation with KTP and UVAR causes a significant increase in the anti-proliferative properties of ketoprofen towards melanoma cells and the co-exposure of melanotic melanoma cells induced apoptosis shown as the mitochondrial membrane breakdown, cell-cycle deregulation, and DNA fragmentation. Moreover, co-treatment led to GSH depletion showing its pro-apoptotic effect dependent on ROS overproduction. The treatment did not show a significant effect on normal cells—melanocytes—which indicates its high selectivity. The results suggest a possible benefit from the use of the ketoprofen and ultraviolet A irradiation as a new concept of melanotic melanoma therapy.

Deregulation of cell cycle and related microRNA expression induced by vinyl chloride monomer in hepatocytes of rats

2021 ◽  
pp. 074823372110155
Author(s):  
Weizhe Pan ◽  
Shengnan Yu ◽  
Jin Jia ◽  
Junyang Hu ◽  
Liang Jie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vinyl Chloride ◽  
Male Rats ◽  
Cell Cycle Distribution ◽  
Vinyl Chloride Monomer ◽  
Dynamic Changes ◽  
Cell Cycle Deregulation ◽  
Change Dynamic ◽  
Related Proteins

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.

scholarly journals Suppression of long noncoding RNA MALAT1 inhibits the development of uveal melanoma via microRNA-608-mediated inhibition of HOXC4

2020 ◽  
Vol 318 (5) ◽  
pp. C903-C912 ◽  
Author(s):  
Shuai Wu ◽  
Han Chen ◽  
Ling Zuo ◽  
Hai Jiang ◽  
Hongtao Yan
Keyword(s):  
Cell Cycle ◽  
Uveal Melanoma ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Melanoma Cells ◽  
Cell Cycle Distribution ◽  
Invasion And Migration ◽  
And Migration

This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.

Unscheduled re-entry into the cell cycle induced by NGF precedes cell death in nascent retinal neurones

2000 ◽  
Vol 113 (7) ◽  
pp. 1139-1148 ◽  
Author(s):  
J.M. Frade
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Ganglion Cells ◽  
Neurotrophin Receptor ◽  
Dependent Manner ◽  
Apoptotic Effect ◽  
Induced Apoptosis

During their early postmitotic life, a proportion of the nascent retinal ganglion cells (RGCs) are induced to die as a result of the interaction of nerve growth factor (NGF) with the neurotrophin receptor p75. To analyse the mechanisms by which NGF promotes apoptosis, an in vitro culture system consisting of dissociated E5 retinal cells was established. In this system, NGF-induced apoptosis was only observed in the presence of insulin and neurotrophin-3, conditions that favour the birth of RGCs and other neurones expressing the glycoprotein G4. The pro-apoptotic effect of NGF on the G4-positive neurones was evident after 10 hours in vitro and was preceded by a significant upregulation of cyclin B2, but not cyclin D1, and the presence of mitotic nuclei in these cells. Brain-derived neurotrophic factor prevented both the increase of cyclin B2 expression in the G4-positive neurones and the NGF-induced cell death. Finally, pharmacologically blocking cell-cycle progression using the cyclin-dependent kinase inhibitor roscovitine prevented NGF-induced cell death in a dose-dependent manner. These results strongly suggest that the apoptotic signalling initiated by NGF requires a driving stimulus manifested by the neuronal birth and is preceded by the unscheduled re-entry of postmitotic neurones into the cell cycle.

α-Tocopheryl succinate alters cell cycle distribution sensitising human osteosarcoma cells to methotrexate-induced apoptosis

2006 ◽  
Vol 232 (2) ◽  
pp. 226-235 ◽  
Author(s):  
Renata Alleva ◽  
Maria Serena Benassi ◽  
Laura Pazzaglia ◽  
Marco Tomasetti ◽  
Nina Gellert ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Distribution ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Tocopheryl Succinate ◽  
Induced Apoptosis

scholarly journals Differential Anti-Proliferative and Anti-Migratory Activities of Ursolic Acid, 3-O-Acetylursolic Acid and Their Combination Treatments with Quercetin on Melanoma Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 894
Author(s):  
Aljawharah AlQathama ◽  
Luying Shao ◽  
Ammar Bader ◽  
Proma Khondkar ◽  
Simon Gibbons ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ursolic Acid ◽  
Morphological Changes ◽  
Melanoma Cells ◽  
Dermal Fibroblasts ◽  
Cell Cycle Distribution ◽  
Parent Molecule ◽  
Combination Treatments ◽  
A375 Cells

We evaluate how 3-acetylation modulates the in vitro activity of ursolic acid in melanoma cells alone or in combination treatments with quercetin. Anti-proliferative studies on A375 cells and adult human dermal fibroblasts included analyses on cell cycle distribution, caspase activity, phosphatidylserine translocation, cell morphology and Bax/Bcl-2 protein expression. Then, 2D and 3D migration of B16F10 cells were studied using scratch and Transwell assays, respectively. Ursolic acid and 3-O-acetylursolic acid have shown similar GI50 on A375 cells (26 µM vs. 32 µM, respectively) significantly increased both early and late apoptotic populations, activated caspases 3/7 (48–72 h), and enhanced Bax whilst attenuating Bcl-2 expression. Ursolic acid caused elevation of the sub-G1 population whilst its 3-acetyl derivative arrested cell cycle at S phase and induced strong morphological changes. Combination treatments showed that ursolic acid and quercetin act synergistically in migration assays but not against cell proliferation. In summary, 3-O-acetylursolic acid maintains the potency and overall apoptotic mechanism of the parent molecule with a more aggressive influence on the morphology of A375 melanoma cells but the 3-acetylation suppresses its anti-migratory properties. We also found that ursolic acid can act in synergy with quercetin to reduce cell migration.

scholarly journals 3,3′-Diindolylmethane: A Promising Sensitizer ofγ-Irradiation

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Wenjing Wang ◽  
Maomin Lv ◽  
Chaoji Huangfu ◽  
Fang Wang ◽  
Jingang Zhang
Keyword(s):  
Cell Cycle ◽  
Phase Cell ◽  
Cell Cycle Distribution ◽  
Effective Treatment Modality ◽  
Intracellular Ros ◽  
M Phase ◽  
Induced Apoptosis ◽  
Mtt Assays ◽  
Mcf 7

Purpose. Radiotherapy is an effective treatment modality in the clinical treatment of breast cancer. The present work investigated the effect of 3,3′-diindolylmethane (DIM) onγ-irradiation sensitizing human breast carcinoma.Methods. Cell survival, intracellular ROS levels, cell cycle distribution, cell apoptosis, and expression of proteins related to apoptosis were measured with MTT assays, flow cytometry, and Western blot analysis, respectively.Results.In vitroDIM plusγ-irradiation arrested the activity of G2/M phase cell cycle, increased intracellular ROS level, significantly suppressed PARP (poly ADP-ribose polymerase), and enhancedγ-irradiation-induced apoptosis, thereby inhibiting the proliferation of MCF-7 cells.Conclusion. These data provide a rationale for the use of DIM as a promising sensitizer ofγ-irradiation.

scholarly journals ERK/GSK3β signaling is involved in atractylenolide I-induced apoptosis and cell cycle arrest in melanoma cells

2015 ◽  
Vol 34 (3) ◽  
pp. 1543-1548 ◽  
Author(s):  
YAN YE ◽  
XIAO-JUAN CHAO ◽  
JIN-FENG WU ◽  
BRIAN CHI-YAN CHENG ◽  
TAO SU ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Melanoma Cells ◽  
Cycle Arrest ◽  
Atractylenolide I ◽  
Induced Apoptosis

scholarly journals T3 preserves ovarian granulosa cells from chemotherapy-induced apoptosis

2012 ◽  
Vol 215 (2) ◽  
pp. 281-289 ◽  
Author(s):  
Cecilia Verga Falzacappa ◽  
Eleonora Timperi ◽  
Barbara Bucci ◽  
Donatella Amendola ◽  
Piero Piergrossi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Hormone ◽  
Granulosa Cells ◽  
Lethal Effect ◽  
Living Cells ◽  
Cell Cycle Distribution ◽  
Ovarian Granulosa Cells ◽  
A Cell ◽  
Induced Apoptosis ◽  
Dying Cells

Infertility is a dramatic and frequent side effect in women who are undergoing chemotherapy. Actual strategies are mainly focused on oocyte cryopreservation, but this is not always a suitable option. Considering the key role that granulosa cells play in follicle life, we studied whether thyroid hormone 3,5,3′-triiodothyronine (T3) protects rat ovarian granulosa cells from chemotherapy-induced apoptosis. To this aim, a cell line was established from fresh isolated rat granulosa cells and named rGROV. Cells were exposed to paclitaxel (PTX) and T3, and apoptosis, cell viability, and cell cycle distribution were analyzed under different conditions. First, the integrity of the steroidogenic pathway was demonstrated, and the presence of thyroid receptors, transporters, and deiodinases was confirmed by quantitative PCR. Cells were then exposed to PTX alone or contemporary to T3. MTT and TUNEL assays revealed that while there was a relevant percentage of dying cells when exposed to PTX (40–60%), the percentage was sensibly reduced (20–30%) in favor of living cells if T3 was present. Cell cycle analysis showed that cells exposed to PTX alone were first collected in G2 and then died by apoptosis; on the other hand, the T3 granted the cells to cycle regularly and survive PTX insult. In addition, western blot and FCM analyses confirmed that caspases activation, casp 3 and Bax, were downregulated by T3 and that Bcl2 and cyclins A and B together with cdk1 were upregulated by T3. In conclusion, we demonstrated that thyroid hormone T3 can counteract the lethal effect of taxol on granulosa cells.

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