scholarly journals Effects of Inhibin A on Apoptosis and Proliferation of Bovine Granulosa Cells

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 367 ◽  
Author(s):  
Huitao Xu ◽  
Adnan Khan ◽  
Shanjiang Zhao ◽  
Huan Wang ◽  
Huiying Zou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Granulosa Cells ◽  
Caspase 3 ◽  
Nuclear Antigen ◽  
Molecular Response ◽  
Dependent Manner ◽  
Inhibin A ◽  
The Impact

Inhibin A is well known for its inhibitory properties against follicle-stimulating hormone (FSH), released through a pituitary–gonadal negative feedback loop to regulate follicular development. Ovarian folliculogenesis, hormonal biosynthesis, and gametogenesis are dependent on inhibins, playing vital roles in promoting or inhibiting cell proliferation. The present study explored the physiological and molecular response of bovine granulosa cells (GCs) to different concentrations of inhibin A in vitro. We treated the primary GCs isolated from ovarian follicles (3–6 mm) with different levels of inhibin A (20, 50, and 100 ng/mL) along with the control (0 ng/mL) for 24 h. To evaluate the impact of inhibin A on GCs, several in vitro cellular parameters, including cell apoptosis, viability, cell cycle, and mitochondrial membrane potential (MMP) were detected. Besides, the transcriptional regulation of pro-apoptotic (BAX, Caspase-3) and cell proliferation (PCNA, CyclinB1) genes were also quantified. The results indicated a significant (p < 0.05) increase in the cell viability in a dose-dependent manner of inhibin A. Likewise, MMP was significantly (p < 0.05) enhanced when GCs were treated with high doses (50, 100 ng/mL) of inhibin A. Furthermore, inhibin A dose (100 ng/mL) markedly improved the progression of the G1 phase of the cell cycle and increased the cell number in the S phase, which was supported by the up-regulation of the proliferating cell nuclear antigen PCNA (20, 50, and 100ng/mL) and CyclinB (100 ng/mL) genes. In addition, higher doses of inhibin A (50 and 100 ng/mL) significantly (p < 0.05) decreased the apoptotic rate in GCs, which was manifested by down regulating BAX and Caspase-3 genes. Conclusively, our study presented a worthy strategy for the first time to characterize the cellular adaptation of bovine GCs under different concentrations of inhibin A. Our results conclude that inhibin A is a broad regulatory marker in GCs by regulating apoptosis and cellular progression.

Lenalidomide Inhibits Proliferation Of Chronic Lymphocytic Leukemia Cells Via a Cereblon/p21WAF1/Cip1-Dependent Mechanism

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4139-4139
Author(s):  
Jessie-Farah Fecteau ◽  
Laura G Corral ◽  
Diahnn Futalan ◽  
Svetlana Gaidarova ◽  
Ila Bharati ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Chronic Lymphocytic Leukemia ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Dependent Manner ◽  
Direct Effects ◽  
P53 Expression ◽  
The Impact

Abstract Lenalidomide has demonstrated clinical activity in patients with chronic lymphocytic leukemia (CLL). However, its mechanism of action is not fully elucidated. Lenalidomide is not directly cytotoxic to CLL cells in vitro, but can alter the capacity of CLL cells to interact with cells in its microenvironment. This has led to the speculation that its primary activity is indirect, although direct effects on CLL cells have been observed. In this study, we examined the direct effects of lenalidomide on CLL cells. We performed transcriptome analysis on primary CLL cell samples exposed to lenalidomide in vitro for 6 and 24hrs and found a significant upregulation of the cyclin-dependent kinase inhibitor p21WAF1/Cip1 (p21), which was also confirmed at the protein level. Since p21 can inhibit the progression of cells from G1 to S phase of the cell cycle, this suggests that lenalidomide may render CLL cells less responsive to proliferation stimuli from the microenvironment. To test this hypothesis, we induced CLL cells to proliferate in vitro using accessory cells made to express CD154 and media containing human interleukin (IL)-4 and IL-10. We monitored for proliferation of CLL cells cultured with and without lenalidomide using carboxyfluorescein succinimidyl ester (CFSE). In repeated experiments, we observed that lenalidomide consistently and significantly inhibited the proliferation of CLL cells in a dose-dependent manner, at concentrations that are achieved in treated patients. Evaluation of the DNA content of CLL cells using propidium iodide and flow cytometry also revealed that lenalidomide significantly decreased the fraction of CLL cells in S and in G2/M phases of the cell cycle and concomitantly increased the percentage of CLL cells in G0/G1 phases. This block in cell proliferation also was accompanied by the upregulation of p21, and the extent of which correlated with the degree to which leukemia-cell proliferation was inhibited. In additional studies, we used small interfering RNA (siRNA) to silence p21 in CLL cells and measured the effect of silencing on cell proliferation in the presence of lenalidomide. We observed that the ability of lenalidomide to inhibit CLL cell proliferation was significantly reduced in CLL cells silenced for p21 compared to CLL cells transfected with control siRNA, supporting a role for p21 expression in mediating the proliferation block induced by lenalidomide. We did not however observe the induction of p53 expression following lenalidomide exposure, suggesting that lenalidomide may upregulate p21 via a p53-independent mechanism. Cereblon (CRBN) is the only known molecular target of lenalidomide. To functionally interrogate the potential role of CRBN in lenalidomide activity on CLL cells, we used siRNA to silence CRBN in primary CLL cells and monitored the impact of silencing on the ability of lenalidomide to upregulate p21 and to inhibit proliferation. We observed lower levels of p21 expression in CRBN-silenced cells exposed to lenalidomide compared to cells transfected with non-specific siRNA, suggesting that CRBN may play a role in p21 upregulation. Furthermore, we observed that CRBN silencing significantly abrogated the anti-proliferative effect of lenalidomide. These results indicate the involvement of CRBN in the anti-proliferative activity of lenalidomide, which is mediated, at least in part, by p21. This study demonstrates that lenalidomide inhibits the proliferation of CLL cells in a CRBN/p21-dependent manner. This direct effect of lenalidomide on CLL cells may account in part for the highly infrequent observation of disease progression in patients receiving long-term maintenance therapy with this agent (Blood, 2013, PMID:23801633). Disclosures: Fecteau: Celgene: Research Funding. Corral:Celgene: Employment. Gaidarova:Celgene: Employment. Cathers:Celgene: Employment. Lopez-Girona:Celgene: Employment. Messmer:Celgene: Research Funding. Kipps:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuiyan Wu ◽  
You Jiang ◽  
Yi Hong ◽  
Xinran Chu ◽  
Zimu Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Acute Lymphoblastic Leukemia ◽  
Caspase 3 ◽  
Lymphoblastic Leukemia ◽  
Rna Seq ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Bet Protein

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL. Methods Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP). Results BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo. Conclusions BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.

scholarly journals The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2178
Author(s):  
Fabio Morandi ◽  
Veronica Bensa ◽  
Enzo Calarco ◽  
Fabio Pastorino ◽  
Patrizia Perri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cell Cycle Progression ◽  
Treatment Strategies ◽  
Annexin V ◽  
Dependent Manner ◽  
Induction Of Apoptosis ◽  
Dose Dependent

Neuroblastoma (NB) is the most common extra-cranial solid tumor of pediatric age. The prognosis for high-risk NB patients remains poor, and new treatment strategies are desirable. The olive leaf extract (OLE) is constituted by phenolic compounds, whose health beneficial effects were reported. Here, the anti-tumor effects of OLE were investigated in vitro on a panel of NB cell lines in terms of (i) reduction of cell viability; (ii) inhibition of cell proliferation through cell cycle arrest; (iii) induction of apoptosis; and (iv) inhibition of cell migration. Furthermore, cytotoxicity experiments, by combining OLE with the chemotherapeutic topotecan, were also performed. OLE reduced the cell viability of NB cells in a time- and dose-dependent manner in 2D and 3D models. NB cells exposed to OLE underwent inhibition of cell proliferation, which was characterized by an arrest of the cell cycle progression in G0/G1 phase and by the accumulation of cells in the sub-G0 phase, which is peculiar of apoptotic death. This was confirmed by a dose-dependent increase of Annexin V+ cells (peculiar of apoptosis) and upregulation of caspases 3 and 7 protein levels. Moreover, OLE inhibited the migration of NB cells. Finally, the anti-tumor efficacy of the chemotherapeutic topotecan, in terms of cell viability reduction, was greatly enhanced by its combination with OLE. In conclusion, OLE has anti-tumor activity against NB by inhibiting cell proliferation and migration and by inducing apoptosis.

scholarly journals Thrombospondin-1 Inhibits Angiogenesis and Promotes Follicular Atresia in a Novel in Vitro Angiogenesis Assay

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1280-1289 ◽  
Author(s):  
Samantha A. Garside ◽  
Christopher R. Harlow ◽  
Stephen G. Hillier ◽  
Hamish M. Fraser ◽  
Fiona H. Thomas
Keyword(s):  
Granulosa Cells ◽  
Caspase 3 ◽  
Polycystic Ovary ◽  
Dependent Manner ◽  
Ovary Syndrome ◽  
Angiogenesis Assay ◽  
Thrombospondin 1 ◽  
In Vitro Angiogenesis ◽  
Dose Dependent

Thrombospondin-1 (TSP-1) is a putative antiangiogenic factor, but its role in regulating physiological angiogenesis is unclear. We have developed a novel in vitro angiogenesis assay to study the effect of TSP-1 on follicular angiogenesis and development. Intact preantral/early antral follicles dissected from 21-d-old rat ovaries were cultured for 6 d in the presence or absence of TSP-1. At the end of the culture period, angiogenic sprouting from the follicles was quantified using image analysis. Follicles were fixed and sectioned, and follicular apoptosis was assessed by immunohistochemistry for activated caspase-3 in granulosa cells. The results showed that TSP-1 inhibited follicular angiogenesis (P &lt; 0.01) and promoted follicular apoptosis (P &lt; 0.001) in a dose-dependent manner. To determine whether the proapoptotic activity of TSP-1 is mediated by direct effects on granulosa cells, isolated granulosa cells were cultured with TSP-1 (0, 10, 100, and 1000 ng/ml) for 48 h. Apoptosis was quantified using a luminescent caspase-3/7 assay. TSP-1 promoted apoptosis of granulosa cells in a dose-dependent manner (P &lt; 0.05), suggesting that TSP-1 can act independently of the angiogenesis pathway to promote follicular apoptosis. These results show that TSP-1 can both inhibit follicular angiogenesis and directly induce apoptosis of granulosa cells. As such, it may have potential as a therapeutic for abnormal ovarian angiogenesis and could facilitate the destruction of abnormal follicles observed in polycystic ovary syndrome.

scholarly journals Inhibition of the aurora kinases suppresses in vitro NT2-D1 cell growth and tumorigenicity

2009 ◽  
Vol 204 (2) ◽  
pp. 135-142 ◽  
Author(s):  
Salvatore Ulisse ◽  
Yannick Arlot-Bonnemains ◽  
Enke Baldini ◽  
Stefania Morrone ◽  
Silvia Carocci ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Transformation ◽  
Germ Cell Tumors ◽  
Aurora Kinase ◽  
Malignant Cell ◽  
Dependent Manner ◽  
Testicular Germ Cell ◽  
Aurora Kinases

The aurora kinase family members, Aurora-A, -B, and -C (listed as AURKA, AURKB and AURKC respectively in the HUGO Database), are serine/threonine kinases involved in the regulation of chromosome segregation and cytokinesis, and alterations in their expression are associated with malignant cell transformation and genomic instability. Deregulation of the expression of the aurora kinases has been shown to occur also in testicular germ cell tumors (TGCTs) identifying them as putative anticancer therapeutic targets. We here evaluated the in vitro effects of MK-0457, an aurora kinases inhibitor, on cell proliferation, cell cycle, ploidy, apoptosis, and tumorigenicity on the TGCT-derived cell line NT2-D1. Treatment with MK-0457 inhibited cell proliferation in a time- and dose-dependent manner, with IC50=17.2±3.3 nM. MK-0457 did not affect the expression of the three aurora kinases, but prevented their ability to phosphorylate substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it, presenting after short time the typical features of apoptotic cells. Cytofluorimetric analysis confirmed that the treatment with MK-0457 for 6 h induced NT2-D1 cells accumulation in the G2/M phase of the cell cycle and the subsequent appearance of sub-G0 nuclei. The latter result was further supported by the detection of caspase-3 activation following 24-h treatment with the inhibitor. Finally, MK-0457 prevented the capability of the NT2-D1 cells to form colonies in soft agar. In conclusion, the above findings demonstrate that inhibition of aurora kinase activity is effective in reducing in vitro growth and tumorigenicity of NT2-D1 cells, and indicate its potential therapeutic value for TGCT treatment.

scholarly journals The impact of IGF1R SNPs on susceptibility to age-related cataract

2019 ◽  
Author(s):  
Yilei Cui ◽  
Xiaoning Yu ◽  
Xin Zhang ◽  
Yelei Tang ◽  
Xiajing Tang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Chinese Population ◽  
Caspase 3 ◽  
S Phase ◽  
Han Chinese ◽  
Human Lens ◽  
Han Chinese Population ◽  
Age Related ◽  
The Impact

Abstract Background: The insulin-like growth factor 1 receptor (IGF1R) gene is essential for lens development, but the impact of IGF1R on age-related cataract(ARC) has not been investigated. This study explored the association between IGF1R single nucleotide polymorphism (SNP) and ARC susceptibility ,and uncover the underlying mechanism in human lens epithelial (HLE) cells. Methods:A total of 1190 unrelated participants ,comprising 690 ARC patients and 550 healthy individuals in Han Chinese population were recruited and genotyped for target SNP. The X2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender. Meanwhile, in the IGF1R knockdown HLE cells, cell proliferation was detected via CCK-8 analysis. Cell cycle and apoptosis were evaluated by flow cytometry,while the expression of cycle- and apoptosis-related molecules were determined via Q-PCR and Western blot. The Caspase-3 activity was measured using its assay kit. Results: The rs1546713 in IGF1R gene was identified（P =0.046，OR：1.606，CI：1.245,2.071）,which shown a significant relevance with ARC risk under the dominant model. The results demonstrated that IGF1R knockdown inhibited cell proliferation by inducing cell cycle arrest at S phase and promoting apoptosis. Mechanistically, the cell cycle blocked at S phase was linked with the alterations of cyclinA , cyclinB, cyclinE and P21,while the pro-apoptosis function was related to stimulate the activation of Caspase-3 activities and the alteration of Caspase-3,Bcl-2 and Bax expression levels. Conclusions: This study first reported that IGF1R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provided new clues to understanding the pathogenic mechanism of ARCs. Notably, IGF1R is likely a potential target for ARC prevention and treatment.

scholarly journals NeosedumosideIII induced Apoptosis of Human Hepatocellular Carcinoma HepG2 cells and SMMC-7721 Cells and Related Mechanism

2021 ◽  
Author(s):  
Xin-Yu Li ◽  
Xin Zhou ◽  
Yu- Liu ◽  
Feng Qiu ◽  
Qing-Qing Zhao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Human Hepatocellular Carcinoma ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Induced Apoptosis

Abstract Purpose: NeosedumosideIII (Neo) is a megastigmanes and belongs to monocyclic sesquiterpenoids compound with antioxidant, anti-inflammatory and other pharmacological activities. In order to explore the anti-cancer effect and possible mechanism of Neo, the study examined the anti-proliferation and apoptosis effect of Neo against human hepatocellular carcinoma HepG2 cells and SMMC-772 cells and related mechanism in vitro. Methods ：The anti-proliferation effect of Neo was detected on HepG2 cells and SMMC-772 cells by MTT assay and IC50 with increasing dose and time. Cell cycle and apoptosis were detected by flow cytometer. The changes of Bcl-2, Bax, Caspase-3, Caspase-8 and Caspase-9 proteins were detected by western blotting.Results ：The results indicated that Neo could inhibited proliferation of HepG2 cells and SMMC-772 cells in vitro and promoted apoptosis, it significantly induced apoptosis of HepG2 cells and SMMC-772 cells arrested cell cycle at G0/G1 phase in a dose-dependent manner, reduce the expression of Bcl-2 protein, and increase the expression of Bax and Caspase-3, Caspase-8 and Caspase-9 proteins. Conclusion：Neo could inhibit proliferation and induce apoptosis of HepG2 cells and SMMC-7721 cells in vivo which suggested that it might be served as a promising candidate for the treatment of liver cancer.

scholarly journals Augmented Cell Signaling by Betanin insights Cancer Cell Remodeling: A Molecular Docking and Experimental Approach

2021 ◽  
Vol 12 (3) ◽  
pp. 3161-3172
Keyword(s):  
Cell Cycle ◽  
Molecular Docking ◽  
Cancer Cell ◽  
In Silico ◽  
Topoisomerase I ◽  
Caspase 3 ◽  
Dependent Manner ◽  
Dna Topoisomerase ◽  
Docking Analysis

Molecular docking analysis has shown to be an important tool for systematically harnessing natural pigment betanin's structural diversity. Natural betanin pigment was used to investigate its anticancer efficacy by in vitro cytotoxicity and cell cycle analysis in A549 lung cancer cell line. Furthermore, docking analysis was used to determine the promising molecular targets for the betanin using different receptor proteins and enzymes responsible for DNA replication (DNA topoisomerases I and II), cell cycle (CDK-6), and in silico apoptotic markers (Bcl-2 and caspase-3) using Glide Schrodinger. In vitro analysis revealed that betanin exerts cytotoxic effects in a cancer cell by inducing apoptosis in a dose-dependent manner with an IC50 value of 17 µM. Furthermore, the cell cycle arrest in response to betanin treatment was strongly observed in flow cytometry analysis. The in silico docking results revealed that betanin exhibited splendid interaction with high affinity against the CDK-6, Bcl-2, and caspase-3 with superior docking scores. Betanin was best docked with DNA topoisomerase II than DNA topoisomerase I. Overall, our report provides scientific evidence that betanin is a novel drug moiety with anticancer property attributes that might be developed and formulated as drug candidate/lead compounds for cancer chemotherapy.

Application of the nuclear factor-κB inhibitor BAY 11-7085 for the treatment of endometriosis: an in vitro study

2007 ◽  
Vol 293 (1) ◽  
pp. E16-E23 ◽  
Author(s):  
Kaei Nasu ◽  
Masakazu Nishida ◽  
Tami Ueda ◽  
Akitoshi Yuge ◽  
Noriyuki Takai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
In Vitro Study ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Phase Cell ◽  
High Recurrence Rate ◽  
Induced Apoptosis

Most of the current medical treatments for endometriosis aim to downregulate estrogen activity. However, a high recurrence rate after medical treatment has been the most significant problem. BAY 11-7085, a soluble inhibitor of NK-κB activation, has been shown to inhibit cell proliferation and induce apoptosis of a variety of cells. To examine the potential application of BAY 11-7085 in the treatment of endometriosis, we investigated the effects of this agent on the cell proliferation and apoptosis of cultured ovarian endometriotic cyst stromal cells (ECSCs) by a modified methylthiazole tetrazolium assay, a 5-bromo-2′-deoxyuridine incorporation assay, and internucleosomal DNA fragmentation assays. The effect of BAY 11-7085 on the cell cycle of ECSCs was also determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSCs with Western blot analysis. BAY 11-7085 significantly inhibited the cell proliferation and DNA synthesis of ECSCs and induced apoptosis and the G0/G1 phase cell cycle arrest of these cells. Additionally, downregulation of the B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-XLexpression with simultaneous activation of caspase-3, -8, and -9 was observed in ECSCs after treatment with BAY 11-7085. These results suggest that BAY 11-7085 induces apoptosis of ECSCs by suppressing antiapoptotic proteins, and that caspase-3-, -8-, and -9-mediated cascades are involved in this mechanism. Therefore, BAY 11-7085 could be used as a therapeutic agent for the treatment of endometriosis.

Toxicity of Industrially Relevant Chlorinated Organic Solvents In Vitro

2013 ◽  
Vol 32 (2) ◽  
pp. 136-145 ◽  
Author(s):  
Catherine McDermott ◽  
James J.A. Heffron
Keyword(s):  
Cell Proliferation ◽  
Organic Solvents ◽  
Caspase 3 ◽  
Free Calcium ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Chlorinated Organic ◽  
Free Calcium Concentration ◽  
Ros Formation

The cytotoxic effects of 4 industrially important chlorinated organic solvents, dichloromethane (DCM), 1,2-dichloroethane (DCE), trichloroethylene (TCE), and tetrachloroethylene (PERC) in vitro, were investigated. Jurkat T cells were exposed to the solvents individually for 72 hours and changes in reactive oxygen species (ROS) formation, cell proliferation, intracellular free calcium concentration ([Ca2+]), and caspase-3 activity were measured. There was a concentration-dependent increase in the ROS formation and intracellular free [Ca2+] following exposure to each of the solvents. This was accompanied by a decrease in the cell proliferation. Solvent potency decreased in the following order: PERC > TCE > DCM > DCE. Caspase-3 activity was increased in a concentration-dependent manner by TCE and PERC but was not significantly altered by DCM or DCE. n-Acetyl-l-cysteine pretreatment showed that changes in the intracellular free [Ca2+] and caspase-3 activity were independent of ROS formation. However, increased ROS formation did play a causal role in the decreased cell proliferation observed.

Sign in / Sign up

Export Citation Format

Share Document