Induction of Apoptosis by the Oolong Tea Polyphenol Theasinensin A through CytochromecRelease and Activation of Caspase-9 and Caspase-3 in Human U937 Cells

2000 ◽  
Vol 48 (12) ◽  
pp. 6337-6346 ◽  
Author(s):  
Min-Hsiung Pan ◽  
Yu-Chih Liang ◽  
Shoei-Yn Lin-Shiau ◽  
Nan-Qun Zhu ◽  
Chi-Tang Ho ◽  
...  
Keyword(s):  
Caspase 3 ◽  
U937 Cells ◽  
Tea Polyphenol ◽  
Caspase 9 ◽  
Oolong Tea ◽  
Induction Of Apoptosis

Omi/HtrA2 and XIAP are components of platelet apoptosis signalling

2013 ◽  
Vol 109 (03) ◽  
pp. 532-539 ◽  
Author(s):  
Jeannine Winkler ◽  
Margaret Rand ◽  
Markus Schmugge ◽  
Oliver Speer
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Transmembrane Potential ◽  
Signalling Pathway ◽  
Ionophore A23187 ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Thrombin Inhibition ◽  
Induction Of Apoptosis ◽  
Apoptotic Proteins

SummaryAlthough platelets possess the hallmarks of apoptosis such as activation of caspases, cytochrome c release and depolarisation of the mitochondrial transmembrane potential (ΔΨm), their entire apoptotic-signalling pathway is not totally understood. Therefore we studied the expression of various apoptotic proteins and found that platelets contain the pro-apoptotic proteins Omi/HtrA2 and Smac/Diablo, as well as their target the X-linked inhibitor of apoptosis XIAP. Omi/HtrA2 and Smac/Diablo were released from mitochondria into the platelet cytosol together with cytochrome c after induction of apoptosis by the Ca2+ ionophore A23187 or the BH3 mimetic ABT-737, and to a lesser extent, after platelet stimulation with collagen and thrombin. Inhibition of Omi/HtrA2 led to decreased levels of activated caspase-3/7 and caspase-9, but did not abolish loss of ΔΨm or prevent release of Omi/HtrA2 from mitochondria. These results indicate that platelets have a functional intrinsic apoptotic-signalling pathway including the pro-apoptotic protease Omi/HtrA2 and its target protein XIAP.

Induction of Apoptosis and Anti-Tumor Effects of a Novel Pan Inhibitor of Bcl-2 and Mcl-1 Apogossypolone (ApoG2) in Multiple Myeloma Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2601-2601
Author(s):  
Jie Lin ◽  
Yongji Wu ◽  
Shujie Wang ◽  
Dajun Yang ◽  
Yongqiang Zhao
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Growth Inhibition ◽  
Caspase 3 ◽  
Xenograft Model ◽  
Caspase 9 ◽  
Dna Ladder ◽  
Myeloma Cells ◽  
Induction Of Apoptosis

Abstract Multiple myeloma remains an incurable malignancy and overall survival has not been improved despite responses to conventional and high-dose chemotherapy. Over-expression of both Bcl-2 and Mcl-1 is frequent in multiple myeloma which renders myeloma cells resistant to apoptosis by chemotherapy, and overexpression is associated with relapse and poorer survival. Inhibition of the anti-apoptotic function of Bcl-2 family member proteins such as Bcl-2 and Mcl-1 represents an attractive new strategy for developing anticancer drugs. Apogossypolone (ApoG2) is a novel derivative of the naturally occurring polyphenolic compound gossypol which has aldehyde moieties removed and further modification to make it pharmaceutically more stable. More particularly, ApoG2 is a potent inhibitor of Mcl-1 and Bcl-2, with Ki value of 25 nM for Mcl-1, 35 nM for Bcl-2, respectively. In this study, trypan blue dye exclusion, Hoechst 33258 staining, DNA ladder formation and annexin-V-PI flow cytometric analysis were used to determine the cellular activities of ApoG2 on cell growth inhibition, cell viability, cell cycle and apoptosis. Cleavage of caspase-3 and caspase-9 was analyzed by colorimetirc assay. Xenograft model of Wus1 cells (from Peking Union Medical College Hospital) in nude mice were used to determine the antitumor activity of compounds. We found that ApoG2 resulted in a dose and time-dependent inhibition of multiple myeloma cell proliferation, with IC50 value to both U266 and Wus1 cells at 0.1 to 0.2 uM at 48 hours after treatment. ApoG2 effectively induced apoptosis of multiple myeloma cells as evidenced by typical morphological changes, transmission electron microscopy, DNA ladder formation and increase in the percentage of cells in subdiploid peak. Colorimetric assays further showed activation of both caspase-3 and caspase-9. In a parallel direct comparison study, ApoG2 was more potent than the parental compound gossypol in both growth inhibition and induction of apoptosis. Of interest, cell cycle analysis of both U266 and Wus1 cells treated with ApoG2 produced a slightly G2 arrest, increasing from 9.7% to 19.6% in U266 cells, and from 9.8% to 31.7% in Wus1 cells, respectively. This was different from gossypol which induced mainly G1 arrest. Preliminary in vivo antitumor activity of ApoG2 was examined in xenograft model of Wus1 cells in nude mice, and growth inhibition (T/C) of 32.7% and 33.4% was obtained at 60 mg/kg, and 40 mg/kg, respectively. In addition, there was no body weight loss for both treated groups in comparison with the vehicle treated mice. Our results demonstrated that a potent pan inhibitor of Bcl-2 and Mcl-1 ApoG2 had significant effect of antiproliferation and induction of apoptosis on multiple myeloma cells in vitro and in vivo. ApoG2 may represent a promising new anticancer agent with a novel molecular mechanism and warrant further investigation as a single agent or in combination for human multiple myeloma with Bcl-2/Mcl-1 overexpression.

DMNQ-S17 inhibits constitutive NF-kappaB activation leading to induction of apoptosis through the activation of caspase-3 in human myeloid leukemia U937 cells

Life Sciences ◽  
2008 ◽  
Vol 83 (13-14) ◽  
pp. 460-467 ◽  
Author(s):  
Min-Jong Park ◽  
Hee-Young Kwon ◽  
Eun-Ok Lee ◽  
Hyo-Jung Lee ◽  
Kwang Seok Ahn ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Caspase 3 ◽  
U937 Cells ◽  
Induction Of Apoptosis ◽  
Nf Kappab

Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells

Blood ◽  
2005 ◽  
Vol 105 (8) ◽  
pp. 3312-3318 ◽  
Author(s):  
Zi Ma ◽  
Ken-ichiro Otsuyama ◽  
Shangqin Liu ◽  
Saeid Abroun ◽  
Hideaki Ishikawa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Caspase 3 ◽  
Herbal Medicines ◽  
Myeloma Cell ◽  
Suppressive Effect ◽  
Caspase 9 ◽  
Myeloma Cells ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

Abstract In the search for a more effective adjuvant therapy to treat multiple myeloma (MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Lian-Jie-Du-Tang (HLJDT), Gui-Zhi-Fu-Ling-Wan (GZFLW), and Huang-Lian-Tang (HLT) on the proliferation and apoptosis of myeloma cells. HLJDT inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Further experiments confirmed that Scutellaria radix was responsible for the suppressive effect of HLJDT on myeloma cell proliferation, and the baicalein in Scutellaria radix showed strong growth inhibition and induction of apoptosis in comparison with baicalin or wogonin. Baicalein as well as baicalin suppressed the survival in vitro of MPC-1- immature myeloma cells rather than MPC-1+ myeloma cells from myeloma patients. Baicalein inhibited the phosphorylation of IkB-α, which was followed by decreased expression of the IL-6 and XIAP genes and activation of caspase-9 and caspase-3. Therefore, HLJDT and Scutellaria radix have an antiproliferative effect on myeloma cells, especially MPC-1- immature myeloma cells, and baicalein may be responsible for the suppressive effect of Scutellaria radix by blocking IkB-α degradation. (Blood. 2005;105:3312-3318)

scholarly journals Induction of Apoptosis by Radix Paeoniae Alba Extract through Cytochrome c Release and the Activations of Caspase-9 and Caspase-3 in HL-60 Cells

2006 ◽  
Vol 29 (6) ◽  
pp. 1082-1086 ◽  
Author(s):  
Kang Beom Kwon ◽  
Eun Kyung Kim ◽  
Mi Jeong Han ◽  
Byung Cheul Shin ◽  
Yong Kweon Park ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Induction Of Apoptosis ◽  
Radix Paeoniae Alba

scholarly journals The Essential Role of Peptidylarginine Deiminases 2 for Cytokines Secretion, Apoptosis, and Cell Adhesion in Macrophage

2020 ◽  
Vol 21 (16) ◽  
pp. 5720
Author(s):  
Hui-Chun Yu ◽  
Chien-Hsueh Tung ◽  
Kuang-Yung Huang ◽  
Hsien-Bin Huang ◽  
Ming-Chi Lu
Keyword(s):  
Cell Adhesion ◽  
Protein Expression ◽  
Caspase 3 ◽  
Interleukin 1 ◽  
Adhesion Assay ◽  
U937 Cells ◽  
Caspase 9 ◽  
Protein Levels ◽  
Tnf Α ◽  
Caspase 2

Objective: The study aims to investigate the functional roles of peptidylarginine deiminase 2 (PADI2) in macrophages. Methods: The clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein-9 nuclease (Cas9) system was used to knockout PADI2 in U937 cells. U937 cells were introduced to differentiate macrophages and were stimulated with lipopolysaccharides (LPS). The protein expression of PADI2, PADI4, and citrullinated proteins were analyzed by Western blotting. The mRNA and protein levels of interleukin 1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using RT-PCR and ELISA, respectively. Cell apoptosis was analyzed using flow cytometry. Cell adhesion assay was performed using a commercially available fibrinogen-coated plate. Results: PADI2 knockout could markedly suppress the PADI2 protein expression, but not the PADI4 protein expression. PADI2 knockout decreased the protein levels of citrullinated nuclear factor κB (NF-κB) p65, but not those of citrullinated histone 3, resulting in the decreased mRNA expression levels of IL-1β and TNF-α in the U937 cells and IL-1β and IL-6 in the differentiated macrophages and the macrophages stimulated with LPS. The cytokines levels of IL-1β, IL-6, and TNF-α were all dramatically decreased in the PADI2 knockout group compared with in the controls. PADI2 knockout prevented macrophages apoptosis via the decreased caspase-3, caspase-2, and caspase-9 activation. PADI2 knockout also impaired macrophages adhesion capacity through the decreased protein levels of focal adhesion kinase (FAK), phospho-FAK, paxillin, phospho-paxillin, and p21-activated kinase 1. Conclusion: This study showed that PADI2 could promote IL-1β, IL-6, and TNF-α production in macrophages, promote macrophage apoptosis through caspase-3, caspase-2, and caspase-9 activation and enhance cell adhesion via FAK, paxillin, and PAK1. Therefore, targeting PADI2 could be used as a novel strategy for controlling inflammation caused by macrophages.

Tpl2 exaggerated ischemic hepatic injury through induction of apoptosis: Downstream of caspase-9

2015 ◽  
Vol 3 (1) ◽  
pp. 339-356
Keyword(s):  
Reperfusion Injury ◽  
Hepatic Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rna Extraction ◽  
Mrna Levels ◽  
Wild Type ◽  
Caspase 9 ◽  
Induction Of Apoptosis

Ischemia-reperfusion injury is a dynamic process that involves the two interrelated phases of local ischemic insult and inflammation-mediated reperfusion injury, and an important cause of liver damage occurring during surgical procedures and represents the main underlying cause of graft dysfunction post-transplantation. This study is a highlight into innate-adaptive immune crosstalk and cell activation cascades that lead to inflammation-mediated injury in livers stressed by ischemia-reperfusion. Tumor Progression Locus 2 (TPL2) is a serine-threonine kinase with essential functions in innate immune cells, where it transmits signals through Toll-like receptors family. To explore the role of Tpl2 in hepatic injury, liver ischemia/reperfusion injury was induced in wild type mice (Tpl2+/+) and in Tpl2-/- mice. They were sacrificed after 3-days post I/R. We determined TPL2 mRNA levels by quantitative PCR (qPCR), DNA and total RNA extraction from tissues was performed using the DNeasy and miRNeasy Kits, the extents of liver and function were studied. Tpl2 knockout mice produce low levels of proinflammatory cytokines expression, reduced release of LDH, ALT and less hepatic injury than wild type mice when exposed to I/R. Interestingly caspase-3 activation was significantly lower in Tpl2-/- mice. These results suggested that Tpl2 directly involved in apoptotic signal at the level of caspase-3 activation downstream of caspase-9, and that Tpl2 contributed to the exaggerated of ischemic liver injury through induction of apoptosis.

Study on Apoptosis of Human Promyelocytic Leukemia HL-60 Cells Induced by Fucosterol via Mitochondrial Pathway

2013 ◽  
Vol 790 ◽  
pp. 611-614 ◽  
Author(s):  
Chen Feng Ji ◽  
Ying Li ◽  
Yu Bin Ji
Keyword(s):  
Laser Scanning ◽  
Caspase 3 ◽  
Mitochondrial Pathway ◽  
Promyelocytic Leukemia ◽  
Caspase 9 ◽  
Mtt Method ◽  
Cyt C ◽  
Induction Of Apoptosis ◽  
Anti Tumor Activity ◽  
Dose Dependent

The purpose of this study is to investigate the effect of fucosterol on the induction of apoptosis and the molecular mechanism involved in Human promyelocytic leukemia HL-60 Cells. HL-60 Cells were treated with different concentrations of fucosterol at different time. MTT method was used to study fucosterol anti-tumor activity. Morphology observation was performed to determine the effects of fucosterol on apoptosis of HL-60 cells. Flow cytometry (FCM) was used to detect the cell cycle. Laser scanning confocal microscope (LSCM) was used to analyze mitochondrial membrane potential (MMP). Western blot was performed to analyze the expressions of Cyt-C, Caspase-9 and Caspase-3. The results showed fucosterol could inhibit the growth of HL-60 cells, and the apoptosis morphology for 48 h treatment was obvious, which showed cell protuberance, cytoplasm concentrated and apoptotic body. Fucosterol treatment for 24 h decreased MMP in dose-dependent manners. It also induced the release of Cyt-C and the activation of Caspase-9 and-3. In conclusion, Fucosterol could induce HL-60 cells apoptosis through a mitochondrial pathway.

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