scholarly journals Colchicine causes prenatal cell toxicity and increases tetraploid risk

2019 ◽  
Author(s):  
Ding Wang ◽  
Yingjun Xie ◽  
Minyi Yan ◽  
Panying Pan ◽  
Yi Liang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amniotic Fluid ◽  
Cell Viability ◽  
Clinical Medicine ◽  
Chorionic Villus ◽  
Toxic Effects ◽  
Small Subset ◽  
Similar Response ◽  
Amniotic Fluid Cells ◽  
M Phase

Abstract Background Colchicine is a clinical medicine used for relief from gout and familial Mediterranean fever. Because of its toxic effects, intravenous injection of colchicine has been banned, but it is still widely administered orally. We assayed the toxic effects of colchicine in cultured primary chorionic villus cells and amniotic fluid cells to interpret its influence on the placenta and foetus. Methods Bright field record and cell count kit 8 were used to value cell viability. Flow cytometer was used to identify cells markers, cell cycle and cell apoptosis. G-banding was used for karyotype analysis for sample genetic and drug effect evaluation. Results Chorionic villus cells and amniotic fluid cells were characterized as mesenchymal cells that share most cell surface markers and have a similar response to colchicine. Colchicine did not induce a decline in cell viability at low concentrations but suppressed cell proliferation by arresting the cell cycle in the G2/M phase and increased the risk of tetraploid generation in a small subset of cases. Conclusions Our study revealed the results of a colchicine-induced toxicity test in prenatal cells and determined the anti-mitotic biologically functional dose and manner of administration that might reduce the risk of tetraploid generation.

scholarly journals Colchicine causes prenatal cell toxicity and increases tetraploid risk

2019 ◽  
Author(s):  
Ding Wang ◽  
Yingjun Xie ◽  
Minyi Yan ◽  
Panying Pan ◽  
Yi Liang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amniotic Fluid ◽  
Cell Viability ◽  
Clinical Medicine ◽  
Chorionic Villus ◽  
Toxic Effects ◽  
Small Subset ◽  
Similar Response ◽  
Amniotic Fluid Cells ◽  
M Phase

Abstract Background Colchicine is a clinical medicine used for relief from gout and familial Mediterranean fever. Because of its toxic effects, intravenous injection of colchicine has been banned, but it is still widely administered orally. We assayed the toxic effects of colchicine in cultured primary chorionic villus cells and amniotic fluid cells to interpret its influence on the placenta and foetus. Methods Bright field record and cell count kit 8 were used to value cell viability. Flow cytometer was used to identify cells markers, cell cycle and cell apoptosis. G-banding was used for karyotype analysis for sample genetic and drug effect evaluation. Results Chorionic villus cells and amniotic fluid cells were characterized as mesenchymal cells that share most cell surface markers and have a similar response to colchicine. Colchicine did not induce a decline in cell viability at low concentrations but suppressed cell proliferation by arresting the cell cycle in the G2/M phase and increased the risk of tetraploid generation in a small subset of cases. Conclusions Our study revealed the results of a colchicine-induced toxicity test in prenatal cells and determined the anti-mitotic biologically functional dose and manner of administration that might reduce the risk of tetraploid generation.

scholarly journals Colchicine causes prenatal cell toxicity and increases tetraploid risk

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ding Wang ◽  
Yingjun Xie ◽  
Minyi Yan ◽  
Qianying Pan ◽  
Yi Liang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amniotic Fluid ◽  
Cell Viability ◽  
Clinical Medicine ◽  
Chorionic Villus ◽  
Toxic Effects ◽  
Small Subset ◽  
Similar Response ◽  
Amniotic Fluid Cells ◽  
M Phase

Abstract Background Colchicine is a clinical medicine used for relief from gout and familial Mediterranean fever. Because of its toxic effects, intravenous injection of colchicine has been banned, but it is still widely administered orally. We assayed the toxic effects of colchicine in cultured primary chorionic villus cells and amniotic fluid cells to interpret its influence on the placenta and foetus. Methods Bright field record and cell count kit 8 were used to value cell viability. Flow cytometer was used to identify cells markers, cell cycle and cell apoptosis. G-banding was used for karyotype analysis for sample genetic and drug effect evaluation. Results Chorionic villus cells and amniotic fluid cells were characterized as mesenchymal cells that share most cell surface markers and have a similar response to colchicine. Colchicine did not induce a decline in cell viability at low concentrations but suppressed cell proliferation by arresting the cell cycle in the G2/M phase and increased the risk of tetraploid generation in a small subset of cases. Conclusions Our study revealed the results of a colchicine-induced toxicity test in prenatal cells and determined the anti-mitotic biologically functional dose and manner of administration that might reduce the risk of tetraploid generation.

scholarly journals Colchicine causes prenatal cell toxicity and increases tetraploid risk

2019 ◽  
Author(s):  
Ding Wang ◽  
Yingjun Xie ◽  
Minyi Yan ◽  
Qianying Pan ◽  
Yi Liang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amniotic Fluid ◽  
Cell Viability ◽  
Clinical Medicine ◽  
Chorionic Villus ◽  
Toxic Effects ◽  
Small Subset ◽  
Similar Response ◽  
Amniotic Fluid Cells ◽  
M Phase

Abstract Background Colchicine is a clinical medicine used for relief from gout and familial Mediterranean fever. Because of its toxic effects, intravenous injection of colchicine has been banned, but it is still widely administered orally. We assayed the toxic effects of colchicine in cultured primary chorionic villus cells and amniotic fluid cells to interpret its influence on the placenta and foetus. Methods Bright field record and cell count kit 8 were used to value cell viability. Flow cytometer was used to identify cells markers, cell cycle and cell apoptosis. G-banding was used for karyotype analysis for sample genetic and drug effect evaluation. Results Chorionic villus cells and amniotic fluid cells were characterized as mesenchymal cells that share most cell surface markers and have a similar response to colchicine. Colchicine did not induce a decline in cell viability at low concentrations but suppressed cell proliferation by arresting the cell cycle in the G2/M phase and increased the risk of tetraploid generation in a small subset of cases. Conclusions Our study revealed the results of a colchicine-induced toxicity test in prenatal cells and determined the anti-mitotic biologically functional dose and manner of administration that might reduce the risk of tetraploid generation.

scholarly journals Colchicine causes prenatal cell toxicity and increases tetraploid risk

2019 ◽  
Author(s):  
Ding Wang ◽  
Yingjun Xie ◽  
Minyi Yan ◽  
Qianying Pan ◽  
Yi Liang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amniotic Fluid ◽  
Cell Viability ◽  
Clinical Medicine ◽  
Chorionic Villus ◽  
Toxic Effects ◽  
Small Subset ◽  
Similar Response ◽  
Amniotic Fluid Cells ◽  
M Phase

Abstract Background Colchicine is a clinical medicine used for relief from gout and familial Mediterranean fever. Because of its toxic effects, intravenous injection of colchicine has been banned, but it is still widely administered orally. We assayed the toxic effects of colchicine in cultured primary chorionic villus cells and amniotic fluid cells to interpret its influence on the placenta and foetus. Methods Bright field record and cell count kit 8 were used to value cell viability. Flow cytometer was used to identify cells markers, cell cycle and cell apoptosis. G-banding was used for karyotype analysis for sample genetic and drug effect evaluation. Results Chorionic villus cells and amniotic fluid cells were characterized as mesenchymal cells that share most cell surface markers and have a similar response to colchicine. Colchicine did not induce a decline in cell viability at low concentrations but suppressed cell proliferation by arresting the cell cycle in the G2/M phase and increased the risk of tetraploid generation in a small subset of cases. Conclusions Our study revealed the results of a colchicine-induced toxicity test in prenatal cells and determined the anti-mitotic biologically functional dose and manner of administration that might reduce the risk of tetraploid generation.

scholarly journals LSD1 Inhibitor 4SC-202 Inducing Apoptosis in Myelodysplastic Syndrome Cells Via NF-κb-HO-1 Pathway

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5415-5415 ◽  
Author(s):  
Weili Wang ◽  
Zhaoyuan Zhang ◽  
Xingyi Kuang ◽  
Jishi Wang
Keyword(s):  
Cell Cycle ◽  
Myelodysplastic Syndrome ◽  
Cell Viability ◽  
Therapeutic Agent ◽  
Conflicts Of Interest ◽  
Myeloid Differentiation ◽  
Histone Lysine ◽  
Lysine Specific Demethylase ◽  
M Phase ◽  
Induced Apoptosis

Aims: Human histone lysine-specific demethylase 1(LSD1) inhibit gene transcription and thereby block myeloid differentiation, apoptosis and cell cycle in AML. 4SC-202, a novel inhibitor of LSD1, is potential therapeutic agent for treating Myelodysplastic syndrome, while its mechanism of action remains unclear. M ainly method : In the study, LSD1 and HO-1 gene expression were detected in MDS/AML patients. After MDS cell line SKM-1 was treated with 4SC-202, cell viability, apoptosis and cell cycle were detected by CCK-8 or FACS. Lastly, western blotting analyzed that the agent caused the change of the related cellular function protein in SKM-1 cells. K ey findings: We found that LSD1 and HO-1 were overexpression in MDS/AML patients. LSD1 inhibitor 4SC-202 inhibited cell viability. The agent induced apoptosis by up-regulated BAX and cleaved caspase3/9 as well as down-regulated BCL-2, arrested cell cycle in the G2/M phase by down-regulated CDK1 and up-regulated p21, as well as inhibited activation of the NF-κB pathway and decreased HO-1. LSD1 and HO-1 expression were decreased after exposure with the NF-κB inhibitor OBY11-7082. Silencing LSD1 by LSD1 siRNA hardly caused apoptosis in SKM-1 cells, while the combination of Bay11-7082 and silencing LSD1 significantly decreased LSD1 and HO-1 expression and further increased apoptosis. While up-regulated HO-1 significantly limited the 4SC-202-induced down-regulation of BCL-2, up-regulation of cleaved caspase 3/9 and suppressed activation of NF-κB pathway as well as thereby attenuated the agent efficacy. S ignificant : In conclusion, LSD1 inhibitor 4SC-202 induced apoptosis through the NF-κB-mediated HO-1 pathway. LSD1 might be a potential target for the treatment of MDS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Methyl Helicterate Inhibits Hepatic Stellate Cell Activation Through Modulation of Apoptosis and Autophagy

2018 ◽  
Vol 51 (2) ◽  
pp. 897-908 ◽  
Author(s):  
Xiao-Lin Zhang ◽  
Zhao-Ni Chen ◽  
Quan-Fang Huang ◽  
Fa-Cheng Bai ◽  
Jin-Lan Nie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Interference ◽  
Cell Viability ◽  
Cell Activation ◽  
Stellate Cell ◽  
Underlying Mechanism ◽  
Autophagic Flux ◽  
Autophagic Vacuoles ◽  
M Phase ◽  
Induced Apoptosis

Background/Aims: Activated hepatic stellate cells (HSCs) are the major source of extracellular matrix (ECM). Therefore inhibiting HSC activation is considered as an effective strategy to inhibit the process of liver fibrosis. This study aimed to investigate the underlying mechanism of methyl helicterate (MH) isolated from Helicteres angustifolia on the activation of HSCs. Methods: HSC-T6 cells were treated with various concentration of MH and autophagy was inhibited by 3-Methyl adenine (3-MA) or RNA interference. Cell viability was observed by MTT assay and cell colony assay. Cell cycle and apoptosis were analyzed using flow cytometry. Autophagic vacuoles were observed by transmission electron microscopy and monodansyl cadaverine (MDC) staining. Moreover, autophagy-related genes and proteins were detected using real-time PCR and Western blot assays, respectively. Results: MH significantly inhibited HSC activation, as evidenced by the inhibition of cell viability, colony formation and the expression of α-SMA and collagen I. MH caused cell cycle arrest in G2/M phase. Moreover, MH significantly induced apoptosis through regulating the mitochondria-dependent pathway and the activity of caspases. MH treatment significantly increased lysosomes and autophagosomes, and enhanced the formation of autophagic vacuoles and autophagic flux. Interestingly, inhibiting autophagy by 3-MA or RNA interference abolished the ability of MH in inhibiting HSC activation. On the other hand, induction of autophagy promoted MH-induced HSC apoptosis. Further study showed that MH-induced HSC apoptosis and autophagy was mediated by the JNK and PI3K/Akt/mTOR pathways. Conclusion: Our results demonstrate that MH-induced HSC apoptosis and autophagy may be one of the important mechanisms for its anti-fibrosis effect.

Inhibition of DNA repair for sensitizing resistant glioma cells to temozolomide

2003 ◽  
Vol 99 (6) ◽  
pp. 1047-1052 ◽  
Author(s):  
Takao Kanzawa ◽  
Joshua Bedwell ◽  
Yasuko Kondo ◽  
Seiji Kondo ◽  
Isabelle M. Germano
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Cell Viability ◽  
Cell Cycle Arrest ◽  
Glioma Cells ◽  
Glioblastoma Cell ◽  
Content Type ◽  
Cycle Arrest ◽  
M Phase ◽  
Fine Print

Object. Temozolomide (TMZ) is a DNA alkylating agent currently used as adjuvant treatment for anaplastic astrocytomas. Its use in managing glioblastoma multiforme has been halted because of the lack of therapeutic effects due to cell resistance. Note that O6-alkylguanine—DNA alkyltranferase (AGT) is a DNA repair enzyme that limits the efficacy of TMZ. In this study the authors investigated the ability of O6-benzylguanine (BG), an AGT inhibitor, to sensitize a glioblastoma cell line resistant to TMZ. Methods. The effects of TMZ alone (100 µg) and after exposure to BG (50 µg) were assessed in two glioblastoma cell lines, U373-MG and T98G, respectively, sensitive and resistant to TMZ. Cell viability was assessed using trypan blue; cell cycle analysis by fluorescence-activated cell sorter; and apoptosis and autophagy by terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and acridine orange staining, respectively. Furthermore, the involvement of an autophagy marker, microtubule-associated light chain 3 (LC3), was assessed. Temozolomide suppressed the growth of and caused cell cycle arrest in the G2—M phase of U373-MG cells but not T98G cells. Exposure to BG prior to TMZ resulted in a significant decrease in cell viability as well as cell cycle arrest in the G2—M phase in T98G cells (p < 0.05). Although apoptosis was not detected on TUNEL staining, programmed cell death Type II (autophagy) was detected after exposure to BG and TMZ in T98G cells. Conclusions. These results indicate that inhibition of AGT by BG can render previously resistant glioma cells sensitive to TMZ treatment. The mechanism of cell demise following BG-TMZ treatment seems to be autophagy and not apoptosis. Combination therapy involving TMZ and an AGT inhibitor may be an effective strategy to treat resistant gliomas.

scholarly journals Antineoplastic Effects of Honokiol on Melanoma

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ruth Guillermo-Lagae ◽  
Sreevidya Santha ◽  
Milton Thomas ◽  
Emily Zoelle ◽  
Jonathan Stevens ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Melanoma ◽  
Cell Viability ◽  
Cell Cycle Progression ◽  
Regulatory Proteins ◽  
M Phase ◽  
Cell Cycle Regulatory Proteins ◽  
In Vitro Effects

Honokiol, a plant lignan has been shown to have antineoplastic effects against nonmelanoma skin cancer developments in mice. In this study, antineoplastic effects of honokiol were investigated in malignant melanoma models. In vitro effects of honokiol treatment on SKMEL-2 and UACC-62 melanoma cells were evaluated by measuring the cell viability, proliferation, apoptosis, cell cycle analysis, and expressions of various proteins associated with cell cycle progression and apoptosis. For the in vivo study, male nude mice inoculated with SKMEL-2 or UACC-62 cells received injections of sesame oil or honokiol for two to seven weeks. In vitro honokiol treatment caused significant decrease in cell viability, proliferation, cell cycle arrest, increased apoptosis, and modulation of apoptotic and cell cycle regulatory proteins. Honokiol caused an accumulation of cells in the G2/M phase of the cell cycle in SKMEL-2 and G0/G1 phase in UACC-62 cells. An elevated level of caspases and PARP were observed in both cell lines treated with honokiol. A decrease in the expression of various cell cycle regulatory proteins was also observed in honokiol treated cells. Honokiol caused a significant reduction of tumor growth in SKMEL-2 and UACC-62 melanoma xenografts. These findings suggest that honokiol is a good candidate for further studies as a possible treatment for malignant melanoma.

scholarly journals PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1136 ◽  
Author(s):  
Masahiro Shinada ◽  
Daiki Kato ◽  
Satoshi Kamoto ◽  
Sho Yoshimoto ◽  
Masaya Tsuboi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Melanoma ◽  
Cell Viability ◽  
Cell Cycle Arrest ◽  
Phase Cell ◽  
Cancer Stemness ◽  
Cycle Arrest ◽  
M Phase ◽  
Canine Tumors ◽  
Induction Of Apoptosis

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed. It is also known to be linked with several aspects of tumor malignancy in some types of human tumors, including invasion, metastasis, and cancer stemness. However, there are few reports on the expression of dog PDPN (dPDPN) in canine tumors, and the association between dPDPN and tumor malignancy has not been elucidated. We identified that 11 out of 18 types of canine tumors expressed dPDPN. Furthermore, 80% of canine malignant melanoma (MM), squamous cell carcinoma, and meningioma expressed dPDPN. Moreover, the expression density of dPDPN was positively associated with the expression of the Ki67 proliferation marker. The silencing of dPDPN by siRNAs resulted in the suppression of cell migration, invasion, stem cell-like characteristics, and cell viability in canine MM cell lines. The suppression of cell viability was caused by the induction of apoptosis and G2/M phase cell cycle arrest. Overall, this study demonstrates that dPDPN is expressed in various types of canine tumors and that dPDPN silencing suppresses cell viability through apoptosis and cell cycle arrest, thus providing a novel biological role for PDPN in tumor progression.

scholarly journals Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair

2021 ◽  
Vol 23 (1) ◽  
pp. 213
Author(s):  
Alessio Malacrida ◽  
Guido Cavaletti ◽  
Mariarosaria Miloso
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Cyclin B ◽  
Cell Cycles ◽  
Protein Levels ◽  
M Phase ◽  
Blotting Technique ◽  
A Cell

Rigosertib is multi-kinase inhibitor that could represent an interesting therapeutic option for non-resectable patients with cholangiocarcinoma, a very aggressive hepatic cancer with limited effective treatments. The Western blotting technique was used to evaluate alterations in the expression of proteins involved in the regulation of the cell cycle of cholangiocarcinoma EGI-1 cells. Our results show an increase in EMI1 and Cyclin B protein levels after Rigosertib treatment. Moreover, the phosphorylation of CDK1 is significantly reduced by Rigosertib, while PLK1 expression increased after 24 h of treatment and decreased after 48 h. Finally, we evaluated the role of p53. Its levels increase after Rig treatment, and, as shown in the cell viability experiment with the p53 inhibitor Pifithrin, its activity is necessary for the effects of Rigosertib against the cell viability of EGI-1 cells. In conclusion, we hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. The CDK1-Cyclin B complex and p53 play an important role, explaining the Block in the G2/M phase of the cell cycle and the effect on cell viability

Sign in / Sign up

Export Citation Format

Share Document