scholarly journals Modulation of Apoptotic Cell Death and Neuroprotective Effects of Glutathione—L-Dopa Codrug Against H2O2-Induced Cellular Toxicity

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 319 ◽  
Author(s):  
Sara Franceschelli ◽  
Paola Lanuti ◽  
Alessio Ferrone ◽  
Daniela Maria Pia Gatta ◽  
Lorenza Speranza ◽  
...  
Keyword(s):  
Cell Lines ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Standard Drug ◽  
Cellular Redox ◽  
Cellular Toxicity ◽  
Ros Formation ◽  
Induced Apoptosis

The L-3,4-dihydroxyphenylalanine (LD) is the gold standard drug currently used to manage Parkinson’s disease (PD) and to control its symptoms. However, LD could cause disease neurotoxicity due to the generation of pro-oxidant intermediates deriving from its autoxidation. In order to overcome this limitation, we have conjugated LD to the natural antioxidant glutathione (GSH) to form a codrug (GSH-LD). Here we investigated the effect of GSH-LD on H2O2-induced cellular toxicity in undifferentiated and differentiated lymphoma U-937 and dopaminergic neuroblastoma SH-SY5Y cell lines, used respectively as models to study the involvement of macrophages/microglia and dopaminergic neurons in PD. We analyzed the effect of GSH-LD on apoptosis and cellular oxidative stress, both considered strategic targets for the prevention and treatment of neurodegenerative diseases. Compared to LD and GSH, GSH-LD had a stronger effect in preventing hydrogen peroxide (H2O2) induced apoptosis in both cell lines. Moreover, GSH-LD was able to preserve cell viability, cellular redox status, gluthation metabolism and prevent reactive oxygen species (ROS) formation, in a phosphinositide 3-kinase (PI3K)/kinase B (Akt)-dependent manner, in a neurotoxicity cellular model. Our findings indicate that the GSH-LD codrug offers advantages deriving from the additive effect of LD and GSH and it could represent a promising candidate for PD treatment.

Neuroprotective Effects of Hypericum perforatum on Trauma Induced by Hydrogen Peroxide in PC12 Cells

2004 ◽  
Vol 32 (03) ◽  
pp. 397-405 ◽  
Author(s):  
Yan-Hua Lu ◽  
Chang-Bin Du ◽  
Jian-Wen Liu ◽  
Wei Hong ◽  
Dong-Zhi Wei
Keyword(s):  
Hydrogen Peroxide ◽  
Pc12 Cells ◽  
Dna Fragmentation ◽  
Hypericum Perforatum ◽  
Dependent Manner ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Mtt Method ◽  
Ros Formation ◽  
Induced Apoptosis

The standard extracts of Hypericum perforatum L. (SEHP), a well-known medicinal plant, are used for the treatment of depression, exhibited upgrading and significant protective effects on the trauma of PC12 cells induced by 200 μM H 2 O 2 in a dose-dependent manner within 24-hour treatment. Cell viability was assessed by the MTT method, and in situ cellular hydrogen peroxide ( H 2 O 2)-induced oxidative stress was examined by measurement of reactive oxygen species (ROS) formation using CDCFH procedures. Intra- and extra-cellular ROS levels decreased significantly to 71.9% and 50.0% of the control at a moderate concentration of 20 μg/ml, respectively, suggesting that SEHP could easily enter the cells and play important roles in reducing ROS levels. Our results were proved by detection of DNA fragmentation and inspection of cell morphology of PC12 cells. SEHP can obviously block DNA fragmentation and prevent the cells from shrinking and turning round of H 2 O 2-induced apoptosis in PC12 cells at concentrations of 10~100 μg/ml. This data suggests SEHP may be a candidate for application in neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease.

scholarly journals Analyzing Cytotoxic and Apoptogenic Properties ofScutellaria litwinowiiRoot Extract on Cancer Cell Lines

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Zahra Tayarani-Najaran ◽  
Seyed Ahmad Emami ◽  
Javad Asili ◽  
Alireza Mirzaei ◽  
Seyed Hadi Mousavi
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Cancer Cell ◽  
Methylene Chloride ◽  
Apoptotic Cell ◽  
Malignant Cell ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Mcf 7

TheScutellariaspecies (Lamiaceae) is used as a source of flavonoids to treat a variety of diseases in traditional medicine. In spite of many reports about the cytotoxic and antitumor effects of some species of this genus, anticancer researches on one of the Iranian speciesS. litwinowiihave not yet been conducted.The cytotoxic properties of total methanol extract ofS. litwinowiiand its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF-7, PC12 and NIH 3T3. Meanwhile, the role of apoptosis in this toxicity was explored. The cells were cultured in DMEM medium and incubated with different concentrations of herb plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak).Scutellaria litwinowiiinhibited the growth of malignant cells in a dose-dependent manner. Among solvent fractions ofS. litwinowii, the methylene chloride fraction was found to be more toxic compared to other fractions. The IC50values of this fraction against AGS, HeLa, MCF-7 and PC12 cell lines after 24 h were determined, 121.2 ± 3.1, 40.9 ± 2.5, 115.9 ± 3.5 and 64.5 ± 3.4μg/ml, respectively.Scutellaria litwinowiiinduced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved inS. litwinowiitoxicity.Scutellaria litwinowiiexerts cytotoxic and proapototic effects in a variety of malignant cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.

Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice

1998 ◽  
Vol 274 (6) ◽  
pp. G1061-G1067 ◽  
Author(s):  
Hitoshi Sawaoka ◽  
Sunao Kawano ◽  
Shingo Tsuji ◽  
Masahiko Tsujii ◽  
Edhi S. Gunawan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Nude Mice ◽  
Tumor Volume ◽  
Malignant Tumors ◽  
Apoptotic Cell ◽  
Dependent Manner ◽  
Cox 2 ◽  
Induced Apoptosis ◽  
Cox 2 Inhibitors

To clarify the role of mitogen-inducible cyclooxygenase (COX-2) in the development of malignant tumors, we investigated the effects of COX-2 inhibitors on the growth of gastric cancer xenografts in nude mice in vivo. MKN45 gastric cancer cells (5 × 106cells/animal) that overexpress COX-2 were inoculated subcutaneously into athymic mice. NS-398, a specific COX-2 inhibitor, or indomethacin, a nonspecific COX-2 inhibitor, was administered orally to animals every day for 20 days. These drugs reduced the tumor volume significantly. Immunohistochemistry using bromodeoxyuridine, nick end labeling, and electron microscopy showed that NS-398 induced apoptosis in cancer cells in a dose-dependent manner and inhibited cancer cell replication slightly. Indomethacin also induced apoptosis and suppressed replication of tumor cells. There was a significant negative correlation between tumor volume and apoptotic cell number within the tumor. These results are consistent with the hypothesis that COX-2 inhibitors suppress growth of gastric cancer xenografts mainly by inducing apoptosis and suppressing replication of the neoplastic cells. It follows that COX-2 plays an important role in the development of gastric cancer.

scholarly journals Role of Luteolin-Induced Apoptosis and Autophagy in Human Glioblastoma Cell Lines

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 879 ◽  
Author(s):  
Hye-Sung Lee ◽  
Bong-Soo Park ◽  
Hae-Mi Kang ◽  
Jung-Han Kim ◽  
Sang-Hun Shin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Glioblastoma Cell ◽  
Related Factors ◽  
Green Pepper ◽  
Real Time Quantitative Pcr ◽  
Anti Inflammatory ◽  
Induced Apoptosis ◽  
Glioblastoma Cell Lines

Background and Objectives: Malignant glioblastoma (GBM) is caused by abnormal proliferation of glial cells, which are found in the brain. The therapeutic effects of surgical treatment, radiation therapy, and chemo-therapy against GBM are relatively poor compared with their effects against other tumors. Luteolin is abundant in peanut shells and is also found in herbs and other plants, such as thyme, green pepper, and celery. Luteolin is known to be effective against obesity and metabolic syndrome. The anti-inflammatory, and anti-cancer activities of luteolin have been investigated. Most studies have focused on the antioxidant and anti-inflammatory effects of luteolin, which is a natural flavonoid. However, the association between the induction of apoptosis by luteolin in GBM and autophagy has not yet been investigated. This study thus aimed to confirm the occurrence of luteolin-induced apoptosis and autophagy in GBM cells and to assess their relationship. Materials and Methods: A172 and U-373MG glioblastoma cell lines were used for this experiment. We confirmed the apoptosis effect of Luteolin on GBM cells using methods such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence, Flow cytometry (FACS) western blot, and real-time quantitative PCR (qPCR). Results: In the luteolin-treated A172 and U-373MG cells, cell viability decreased in a concentration- and time-dependent manner. In addition, in A172 and U-373MG cells treated with luteolin at concentrations greater than 100 μM, nuclear fragmentation, which is a typical morphological change characterizing apoptosis, as well as fragmentation of caspase-3 and Poly (ADP-ribose) polymerase (PARP), which are apoptosis-related factors, were observed. Autophagy was induced after treatment with at least 50 μM luteolin. Inhibition of autophagy using 3MA allowed for a low concentration of luteolin to more effectively induce apoptosis in A172 and U-373MG cells. Conclusions: Results showed that luteolin induces apoptosis and autophagy and that the luteolin-induced autophagy promotes cell survival. Therefore, an appropriate combination therapy involving luteolin and an autophagy inhibitor is expected to improve the prognosis of GBM treatment.

scholarly journals Cyclovirobuxine D Induces Apoptosis and Mitochondrial Damage in Glioblastoma Cells Through ROS-Mediated Mitochondrial Translocation of Cofilin

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Zhang ◽  
Ruoqiu Fu ◽  
Dongyu Duan ◽  
Ziwei Li ◽  
Bin Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Oxidant Stress ◽  
Mitochondrial Damage ◽  
Dependent Manner ◽  
Mitochondrial Translocation ◽  
Mitochondrial Superoxide ◽  
Human Astrocytes ◽  
Anti Cancer ◽  
Normal Human ◽  
Induced Apoptosis

BackgroundCyclovirobuxine D (CVBD), a steroidal alkaloid, has multiple pharmacological activities, including anti-cancer activity. However, the anti-cancer effect of CVBD on glioblastoma (GBM) has seldom been investigated. This study explores the activity of CVBD in inducing apoptosis of GBM cells, and examines the related mechanism in depth.MethodsGBM cell lines (T98G, U251) and normal human astrocytes (HA) were treated with CVBD. Cell viability was examined by CCK-8 assay, and cell proliferation was evaluated by cell colony formation counts. Apoptosis and mitochondrial superoxide were measured by flow cytometry. All protein expression levels were determined by Western blotting. JC-1 and CM-H2DCFDA probes were used to evaluate the mitochondrial membrane potential (MMP) change and intracellular ROS generation, respectively. The cell ultrastructure was observed by transmission electron microscope (TEM). Colocalization of cofilin and mitochondria were determined by immunofluorescence assay.ResultsCVBD showed a greater anti-proliferation effect on the GBM cell lines, T98G and U251, than normal human astrocytes in dose- and time-dependent manners. CVBD induced apoptosis and mitochondrial damage in GBM cells. We found that CVBD led to mitochondrial translocation of cofilin. Knockdown of cofilin attenuated CVBD-induced apoptosis and mitochondrial damage. Additionally, the generation of ROS and mitochondrial superoxide was also induced by CVBD in a dose-dependent manner. N-acetyl-L-cysteine (NAC) and mitoquinone (MitoQ) pre-treatment reverted CVBD-induced apoptosis and mitochondrial damage. MitoQ pretreatment was able to block the mitochondrial translocation of cofilin caused by CVBD.ConclusionsOur data revealed that CVBD induced apoptosis and mitochondrial damage in GBM cells. The underlying mechanism is related to mitochondrial translocation of cofilin caused by mitochondrial oxidant stress.

scholarly journals Role of mitochondrial glucocorticoid receptor in glucocorticoid-induced apoptosis

2006 ◽  
Vol 203 (1) ◽  
pp. 189-201 ◽  
Author(s):  
Ronit Vogt Sionov ◽  
Orly Cohen ◽  
Shlomit Kfir ◽  
Yael Zilberman ◽  
Eitan Yefenof
Keyword(s):  
T Cell ◽  
Glucocorticoid Receptor ◽  
Cell Lines ◽  
Cell Types ◽  
Thymic Epithelial Cells ◽  
Dependent Manner ◽  
Localization Signal ◽  
Induced Apoptosis ◽  
T Cell Lines

The mechanisms by which glucocorticoid receptor (GR) mediates glucocorticoid (GC)-induced apoptosis are unknown. We studied the role of mitochondrial GR in this process. Dexamethasone induces GR translocation to the mitochondria in GC-sensitive, but not in GC-resistant, T cell lines. In contrast, nuclear GR translocation occurs in all cell types. Thymic epithelial cells, which cause apoptosis of the PD1.6 T cell line in a GR-dependent manner, induce GR translocation to the mitochondria, but not to the nucleus, suggesting a role for mitochondrial GR in eliciting apoptosis. This hypothesis is corroborated by the finding that a GR variant exclusively expressed in the mitochondria elicits apoptosis of several cancer cell lines. A putative mitochondrial localization signal was defined to amino acids 558–580 of human GR, which lies within the NH2-terminal part of the ligand-binding domain. Altogether, our data show that mitochondrial and nuclear translocations of GR are differentially regulated, and that mitochondrial GR translocation correlates with susceptibility to GC-induced apoptosis.

Fas/APO-1 (CD95)–Mediated Apoptosis Is Activated by Interferon-γ and Interferon- in Interleukin-6 (IL-6)–Dependent and IL-6–Independent Multiple Myeloma Cell Lines

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2914-2923 ◽  
Author(s):  
Helena Spets ◽  
Patrik Georgii-Hemming ◽  
Jan Siljason ◽  
Kenneth Nilsson ◽  
Helena Jernberg-Wiklund
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Poor Response ◽  
Antigen Expression ◽  
Myeloma Cell ◽  
Interferon Γ ◽  
Dependent Manner ◽  
Multiple Myeloma Cell ◽  
Ifn Γ ◽  
Induced Apoptosis

Abstract A poor response to Fas-induced apoptosis is evident in some multiple myeloma (MM) cell lines and primary cells. In this study, we have examined the possibility to increase the sensitivity to Fas-induced apoptosis by pretreatment of MM cells with interferon-γ (IFN-γ) or interferon- (IFN-). Both IFN-γ and IFN- markedly increased the Fas-induced apoptosis in all cell lines tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-1958 cell lines, pretreatment with either IFN-γ or IFN- also inhibited proliferation in a dose-dependent manner. In contrast, IFN-γ activation of the Fas death pathway in the U-266-1984 cells was not accompanied by growth inhibition. Incubation with the IFNs increased the Fas antigen expression in one of three cell lines but did not alter the expression of Bcl-2 or Bax. The IFNs are important regulators of growth and survival in MM cells. Our results suggest that activation of Fas-mediated apoptosis is a novel mechanism by which the IFNs exert inhibitory effects on MM cells. © 1998 by The American Society of Hematology.

scholarly journals Dihydrochalcone Derivative Induces Breast Cancer Cell Apoptosis via Intrinsic, Extrinsic, and ER Stress Pathways but Abolishes EGFR/MAPK Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Wasitta Rachakhom ◽  
Patompong Khaw-on ◽  
Wilart Pompimon ◽  
Ratana Banjerdpongchai
Keyword(s):  
Breast Cancer ◽  
Er Stress ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Annexin V ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Induced Apoptosis ◽  
Mcf 7

Dihydrochalcone derivatives are active compounds that have been purified from the Thai medicinal plant Cyathostemma argenteum. The objectives of this study were to investigate the effects of two dihydrochalcone derivatives on human breast cancer MDA-MB-231 and MCF-7 cell proliferation and to study the relevant mechanisms involved. The two dihydrochalcone derivatives are 4′,6′-dihydroxy-2′,4-dimethoxy-5′-(2″-hydroxybenzyl)dihydrochalcone (compound 1) and calomelanone (2′,6′-dihydroxy-4,4′-dimethoxydihydrochalcone, compound 2), both of which induced cytotoxicity toward both cell lines in a dose-dependent manner by using MTT assay. Treatment with both derivatives induced apoptosis as determined by annexin V-FITC/propidium iodide employing flow cytometry. The reduction of mitochondrial transmembrane potential (staining with 3,3′-dihexyloxacarbocyanine iodide, DiOC6, employing a flow cytometer) was established in the compound 1-treated cells. Compound 1 induced caspase-3, caspase-8, and caspase-9 activities in both cell lines, as has been determined by specific colorimetric substrates and a spectrophotometric microplate reader which indicated the involvement of both the extrinsic and intrinsic pathways. Calcium ion levels in mitochondrial and cytosolic compartments increased in compound 1-treated cells as detected by Rhod-2AM and Fluo-3AM intensity, respectively, indicating the involvement of the endoplasmic reticulum (ER) stress pathway. Compound 1 induced cell cycle arrest via enhanced atm and atr expressions and by upregulating proapoptotic proteins, namely, Bim, Bad, and tBid. Moreover, compound 1 significantly inhibited the EGFR/MAPK signaling pathway. In conclusion, compound 1 induced MDA-MB-231 and MCF-7 cell apoptosis via intrinsic, extrinsic, and ER stress pathways, whereas it ameliorated the EGFR/MAPK pathway in the MCF-7 cell line. Consequently, it is believed that compound 1 could be effectively developed for cancer treatments.

scholarly journals Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ce Shi ◽  
Wenjia Lan ◽  
Zhenkun Wang ◽  
Dongguang Yang ◽  
Jia Wei ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tumor Growth ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Dependent Manner ◽  
Nude Mouse Model ◽  
Hematopoietic Malignancy ◽  
Induced Apoptosis ◽  
Anti Tumor Activity

Abstract Background Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. Methods ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. Results ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. Conclusions The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

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