scholarly journals Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest

Tumor Biology ◽  
2017 ◽  
Vol 39 (11) ◽  
pp. 101042831773145 ◽  
Author(s):  
Fatima Abdelmutaal Ahmed Omer ◽  
Najihah Binti Mohd Hashim ◽  
Mohamed Yousif Ibrahim ◽  
Firouzeh Dehghan ◽  
Maizatulakmal Yahayu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Line ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Intrinsic Apoptosis ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway.

Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

2001 ◽  
Vol 280 (1) ◽  
pp. L10-L17 ◽  
Author(s):  
Han-Ming Shen ◽  
Zhuo Zhang ◽  
Qi-Feng Zhang ◽  
Choon-Nam Ong
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Alveolar Macrophages ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Parp Cleavage ◽  
Oxygen Species ◽  
Caspase Activation ◽  
Caspase 9 ◽  
Induced Apoptosis

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

scholarly journals Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Christopher Platen ◽  
Stephan Dreschers ◽  
Jessica Wappler ◽  
Andreas Ludwig ◽  
Stefan Düsterhöft ◽  
...  
Keyword(s):  
Cell Death ◽  
Bacterial Infections ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Dependent Manner ◽  
Intrinsic Apoptosis ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway

Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphiregulin (AREG) is increasingly expressed on the cell surface of neonatal monocytes, resulting in remarkably higher soluble AREG levels after proteolytic shedding. In this study, we found that E. coli-infected neonatal monocytes show an increased phosphorylation of ERK, increased expression of Bcl-2 and Bcl-XL, and reduced levels of cleaved caspase-3 and caspase-9 compared to adult monocytes. In both cell types, additional stimulation with soluble AREG further increased ERK activation and expression of Bcl-2 and Bcl-XL and reduced levels of cleaved caspase-3 and caspase-9 in an EGFR-dependent manner. These data suggest that reduced PICD of neonatal monocytes could be due to reduced intrinsic apoptosis and that AREG can promote protection against PICD. This reduction of the intrinsic apoptosis pathway in neonatal monocytes could be relevant for severely prolonged inflammatory responses of neonates.

Synthesis and Biological Evaluation of Novel 2-imino-4-thiazolidinones as Potential Antitumor Agents for Glioblastoma

2021 ◽  
Vol 17 ◽  
Author(s):  
José Coan Campos ◽  
Patrick Teixeira Campos ◽  
Nathalia Stark Pedra ◽  
Natália Pontes Bona ◽  
Mayara Sandrielly Soares ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Cell Line ◽  
Caspase 3 ◽  
Antitumor Agents ◽  
G1 Phase ◽  
Oxygen Species ◽  
C6 Cell Line ◽  
Potential Antitumor

Aims: The purpose of our study was to explore the molecular hybridization between 2-imino-4-thizolidione and piridinic scaffolds and its potential antitumor activity. Background: Glioblastoma is the most aggressive glioma tumor clinically diagnosed malignant and highly recurrent primary brain tumor type. The standard of treatment for a glioblastoma is surgery, followed by radiation and chemotherapy using temozolomide. However, the chemoresistance has become the main barrier to treatment success. 2-imino-4-thiazolidinones are an important class of heterocyclic compounds that feature anticancer activity; however the antiglioblastoma activity is yet to be explored. Objective: To synthesize and characterize a series of novel 2-imino-4-thiazolidinones and evaluate their antiglioblastoma activity. Method: The 2-imino-4-thiazolidinone (5a-p) was synthesized according to the literature with modifications. Compounds were identified and characterized using spectroscopic analysis and X-ray diffraction. The antitumor activity was analyzed by 3-(4,5- dimethyl)-2,5-diphenyltetrazolium bromide (MTT) assay both in primary astrocyte and glioma (C6). Apoptosis and cell cycle phase were determined by flow cytometry analysis. The expression of caspase-3/7 was measured by luminescence assay. Oxidative stress parameters as: determination of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, catalase (CAT) activity and total sulfhydryl content quantification were analyzed by colorimetric assays according to literature. Results: Among sixteen synthesized compounds, three displayed potent antitumor activities against tested glioblastoma cell line showed IC50 values well below the standard drug temozolomide. Therefore, compounds 5a, 5l and 5p were evaluated using cell cycle and death analysis, due to potent toxicity (2.17±1.17, 6.24±0.59, 2.93±1.12µM, respectively) in C6 cell line. The mechanism of action studies demonstrated that 5a and 5l induced apoptosis significantly increase the percentage of cells in Sub-G1 phase in the absence of necrosis. Consistent with these results, caspase-3/7 assay revealed that 5l presents pro-apoptotic activity due to the significant stimulation of caspases-3/7. Moreover, 5a, 5l and 5p increased antioxidant defense and decreased reactive oxygen species (ROS) production. Conclusion: The compounds were synthesized with good yield and three of these presented (5a, 5l and 5p) good cytotoxicity against C6 cell line. Both affected cell cycle distribution via arresting more C6 cell line at Sub-G1 phase promoting apoptosis. Furthermore, 5a, 5l and 5p modulated redox status. These findings suggest that these compounds can be considered as promising lead molecules for further development of potential antitumor agents.

scholarly journals Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway

2021 ◽  
Vol 22 (8) ◽  
pp. 4056
Author(s):  
Yuan-Yen Chang ◽  
Yi-Ju Lee ◽  
Min-Yen Hsu ◽  
Meilin Wang ◽  
Shang-Chun Tsou ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Retinal Pigment Epithelium ◽  
Caspase 3 ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Sodium Iodate ◽  
Apoptosis Pathway ◽  
Underlying Mechanisms

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.

scholarly journals Polygonum cuspidatumExtract Induces Anoikis in Hepatocarcinoma Cells Associated with Generation of Reactive Oxygen Species and Downregulation of Focal Adhesion Kinase

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Bing Hu ◽  
Hong-Mei An ◽  
Ke-Ping Shen ◽  
Hai-Yan Song ◽  
Shan Deng
Keyword(s):  
Reactive Oxygen Species ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Caspase 3 ◽  
Chinese Herb ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Polygonum Cuspidatum ◽  
Caspase 9 ◽  
Hepatocarcinoma Cells

Anoikis has been recognized as a potential target for anticancer therapy.Polygonum cuspidatum(Huzhang) is a frequently used Chinese herb in hepatocarcinoma. In present study, we evaluated the effects ofPolygonum cuspidatumextract (PCE) in hepatocarcinoma cells in suspension. The results showed that PCE inhibited the proliferation of hepatocarcinoma cells in suspension in a dose- and time-dependent manner. PCE also inhibited anchorage-independent growth of hepatocarcinoma cells in soft agar. PCE induced anoikis in human hepatocarcinoma Bel-7402 cells accompanied by caspase-3 and caspase-9 activation and poly(ADP-ribose) polymerase cleavage, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. In addition, PCE treatment induced intracellular reactive oxygen species (ROS) production in Bel-7402 cells. NAC, an ROS scavenger, partially attenuated PCE-induced anoikis and activation of caspase-3 and caspase-9. Furthermore, PCE inhibited expression of focal adhesion kinase (FAK) in Bel-7402 cells. Overexpression of FAK partially abrogated PCE-induced anoikis. These data suggest that PCE may inhibit suspension growth and induce caspase-mediated anoikis in hepatocarcinoma cells and may relate to ROS generation and FAK downregulation. The present study provides new insight into the application of Chinese herb for hepatocarcinoma treatment.

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