scholarly journals ROS-Mediated Apoptosis and Genotoxicity Induced by Palladium Nanoparticles in Human Skin Malignant Melanoma Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Saud Alarifi ◽  
Daoud Ali ◽  
Saad Alkahtani ◽  
Rafa S. Almeer
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Malignant Melanoma ◽  
Cell Cycle Arrest ◽  
Human Skin ◽  
Palladium Nanoparticles ◽  
Molecular Mechanisms ◽  
Time Dependent ◽  
Cycle Arrest ◽  
A375 Cells

The present work was designed to investigate the effect of palladium nanoparticles (PdNPs) on human skin malignant melanoma (A375) cells, for example, induction of apoptosis, cytotoxicity, and DNA damage. Diseases resulting from dermal exposure may have a significant impact on human health. There is a little study that has been reported on the toxic potential of PdNPs on A375. Cytotoxic potential of PdNPs (0, 5, 10, 20, and 40 μg/ml) was measured by tetrazolium bromide (MTT assay) and NRU assay in A375 cells. PdNPs elicited concentration and time-dependent cytotoxicity, and longer exposure period induced more cytotoxicity as measured by MTT and NRU assay. The molecular mechanisms of cytotoxicity through cell cycle arrest and apoptosis were investigated by AO (acridine orange)/EtBr (ethidium bromide) stain and flow cytometry. PdNPs not only inhibit proliferation of A375 cells in a dose- and time-dependent model but also induce apoptosis and cell cycle arrest at G2/M phase (before 12 h) and S phase (after 24 h). The induction of oxidative stress in A375 cells treated with above concentration PdNPs for 24 and 48 h increased ROS level; on the other hand, glutathione level was declined. Apoptosis and DNA damage was significantly increased after treatment of PdNPs. Considering all results, PdNPs showed cytotoxicity and genotoxic effect in A375 cells.

The cytotoxic effect of oxybuprocaine on human corneal epithelial cells by inducing cell cycle arrest and mitochondria-dependent apoptosis

2016 ◽  
Vol 36 (8) ◽  
pp. 765-775 ◽  
Author(s):  
W-Y Fan ◽  
D-P Wang ◽  
Q Wen ◽  
T-J Fan
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cytotoxic Effect ◽  
Molecular Mechanisms ◽  
Time Dependent ◽  
Plasma Membrane Permeability ◽  
Topical Anesthetic ◽  
Corneal Epithelial ◽  
Cycle Arrest

Oxybuprocaine (OBPC) is a widely used topical anesthetic in eye clinic, and prolonged and repeated usage of OBPC might be cytotoxic to the cornea, especially to the outmost corneal epithelium. In this study, we characterized the cytotoxic effect of OBPC on human corneal epithelial (HCEP) cells and investigated its possible cellular and molecular mechanisms using an in vitro model of non-transfected HCEP cells. Our results showed that OBPC at concentrations ranging from 0.025% to 0.4% had a dose- and time-dependent cytotoxicity to HCEP cells. Moreover, OBPC arrested the cells at S phase and induced apoptosis of these cells by inducing plasma membrane permeability, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation. Furthermore, OBPC could trigger the activation of caspase-2, -3, and -9, downregulate the expression of Bcl-xL, upregulate the expression of Bax along with the cytoplasmic amount of mitochondria-released apoptosis-inducing factor, and disrupt mitochondrial transmembrane potential. Our results suggest that OBPC has a dose- and time-dependent cytotoxicity to HCEP cells by inducing cell cycle arrest and cell apoptosis via a death receptor-mediated mitochondria-dependent proapoptotic pathway, and this novel finding provides new insights into the acute cytotoxicity and its toxic mechanisms of OBPC on HCEP cells.

scholarly journals Isothiocyanate-induced Cell Cycle Arrest in a Novel In Vitro Exposure Protocol of Human Malignant Melanoma (A375) Cells

2019 ◽  
Vol 39 (2) ◽  
pp. 591-596 ◽  
Author(s):  
THEODORA MANTSO ◽  
IOANNIS ANESTOPOULOS ◽  
ELEFTHERIA LAMPRIANIDOU ◽  
IOANNIS KOTSIANIDIS ◽  
AGLAIA PAPPA ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Melanoma ◽  
Cell Cycle Arrest ◽  
Human Malignant Melanoma ◽  
Cycle Arrest ◽  
In Vitro Exposure ◽  
A375 Cells

Cucurbitacin IIb from Ibervillea sonorae Induces Apoptosis and Cell Cycle Arrest via STAT3 Inhibition

2020 ◽  
Vol 20 (10) ◽  
pp. 1188-1196
Author(s):  
Heriberto Torres-Moreno ◽  
Maria C. Marcotullio ◽  
Carlos Velazquez ◽  
Víctor M. Arenas-Luna ◽  
Salomón Hernández-Gutiérrez ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Dna Damage ◽  
Membrane Potential ◽  
Cell Cycle Arrest ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Cyclin B1 ◽  
Cycle Arrest

Background: Cucurbitacin IIb (CIIb) from Ibervillea sonorae has a high capacity to suppress cancer cell proliferation and induce apoptosis. This study investigated the molecular mechanisms related to the antiproliferative and apoptosis induction capacity of CIIb in HeLa cells. Materials and Methods: The cell viability and anti-proliferative effect of CIIb were evaluated by using the trypan blue exclusion assay. The effect of CIIb on the mitochondrial membrane potential was determined by flow cytometry using JC-1. The activity of caspase-3 and caspase-9 was evaluated by flow cytometry using commercial kits. The effect of CIIb on the cell cycle was investigated using Fluorescence-Activated Cell Sorting (FACS) analysis. Western blot analysis was used to evaluate both the inhibitory effect of CIIb on the STAT3 signaling pathway and cyclin –B1, and DNA damage by the comet assay. Results: CIIb triggers disruption of the mitochondrial membrane potential (Δψm) and consequently activated the caspases -3 and -9, as a result of the activation of the intrinsic pathway of the apoptosis. Likewise, the CIIbinduced cell cycle was arrested in S and G2/M after 24h of treatment. CIIb also reduced the expression of STAT3 and cyclin –B1. Finally, CIIb produced an antiproliferative effect at 48 and 72 h, inducing DNA damage. Conclusion: These results demonstrate CIIb-induced apoptosis and cell cycle arrest in HeLa through the inhibition of STAT3.

scholarly journals Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 275 ◽  
Author(s):  
Wenjing Liu ◽  
Xiaona Liu ◽  
Zhaohai Pan ◽  
Dan Wang ◽  
Minjing Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Melanoma ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Melanoma B16 ◽  
Cycle Arrest ◽  
A375 Cells

Malignant melanoma is the most lethal type of skin cancer. Previous studies have shown that ailanthone has potent antitumor activity in a variety of cell lines. However, the anti-tumor effect of ailanthone on malignant melanoma remains unclear. To investigate the anti-tumor mechanisms of ailanthone in human melanoma B16 and mouse melanoma A375 cells, the cell counting kit-8 assay, colony formation assay, DNA content analysis, Hoechst 33258, and Annexin V-FITC/PI staining were used to assess cell proliferation, cell cycle distribution, and cell apoptosis, respectively. Western blotting was performed to evaluate the expression of cell cycle- and apoptosis-related proteins and regulatory molecules. The results showed that ailanthone significantly inhibited melanoma B16 and A375 cell proliferation as well as remarkably induced cell cycle arrest at the G0–G1 phase in B16 cells and the G2–M phase in A375 cells in a dose-dependent manner. Further investigation revealed that ailanthone promoted the expression of p21 and suppressed the expression of cyclin E in B16 cells or cyclin B in A375 cells through the PI3K-Akt signaling pathway. In addition, ailanthone induced B16 and A375 cell apoptosis via a caspase-dependent mechanism. Further studies showed that ailanthone remarkably downregulated Bcl-2 and upregulated Apaf-1 and Bax, and subsequently increased mitochondrial membrane permeabilization and released cytochrome c from the mitochondria in B16 cells and A375 cells. Taken together, ailanthone induces cell cycle arrest via the PI3K-Akt signaling pathway as well as cell apoptosis via the mitochondria-mediated apoptotic signaling pathway. Ailanthone may be potentially utilized as an anti-tumor agent in the management of malignant melanoma.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

scholarly journals Design, Synthesis and Pharmacological Evaluation of Three Novel Dehydroabietyl Piperazine Dithiocarbamate Ruthenium (II) Polypyridyl Complexes as Potential Antitumor Agents: DNA Damage, Cell Cycle Arrest and Apoptosis Induction

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1453
Author(s):  
Haoran Wang ◽  
Jianhua Wei ◽  
Hong Jiang ◽  
Ye Zhang ◽  
Caina Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Antitumor Agents ◽  
Mechanistic Study ◽  
Ros Generation ◽  
Polypyridyl Complexes ◽  
Expression Levels ◽  
Cycle Arrest ◽  
Study Results

The use of cisplatin is severely limited by its toxic side-effects, which has spurred chemists to employ different strategies in the development of new metal-based anticancer agents. Here, three novel dehydroabietyl piperazine dithiocarbamate ruthenium (II) polypyridyl complexes (6a–6c) were synthesized as antitumor agents. Compounds 6a and 6c exhibited better in vitro antiproliferative activity against seven tumor cell lines than cisplatin, they displayed no evident resistance in the cisplatin-resistant cell line A549/DPP. Importantly, 6a effectively inhibited tumor growth in the T-24 xenograft mouse model in comparison with cisplatin. Gel electrophoresis assay indicated that DNA was the potential targets of 6a and 6c, and the upregulation of p-H2AX confirmed this result. Cell cycle arrest studies demonstrated that 6a and 6c arrested the cell cycle at G1 phase, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of cyclin E. In addition, 6a and 6c caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-9, cytochrome c, intracellular Ca2+ release, reactive oxygen species (ROS) generation and the downregulation of Bcl-2. These mechanistic study results suggested that 6a and 6c exerted their antitumor activity by inducing DNA damage, and consequently causing G1 stage arrest and the induction of apoptosis.

scholarly journals ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53.

2002 ◽  
Vol 277 (23) ◽  
pp. 21110 ◽  
Author(s):  
Damu Tang ◽  
Dongcheng Wu ◽  
Atsushi Hirao ◽  
Jill M. Lahti ◽  
Lieqi Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Erk Activation ◽  
Cycle Arrest
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