Celastrol Induces Mitochondria-Mediated Apoptosis in Hepatocellular Carcinoma Bel-7402 Cells

2015 ◽  
Vol 43 (01) ◽  
pp. 137-148 ◽  
Author(s):  
Pei-Pei Li ◽  
Wei He ◽  
Ping-Fan Yuan ◽  
Sha-Sha Song ◽  
Jing-Tao Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Mitochondrial Pathway ◽  
Time Dependent ◽  
Tripterygium Wilfordii ◽  
Caspase 9 ◽  
Chinese Medicinal Herb ◽  
Dependent Growth ◽  
Induced Apoptosis

Celastrol is a natural terpenoid isolated from Tripterygium wilfordii, a well-known Chinese medicinal herb that presents anti-proliferative activities in several cancer cell lines. Here, we investigated whether celastrol induces apoptosis on hepatocellular carcinoma Bel-7402 cells and further explored the underlying molecular mechanisms. Celastrol caused a dose- and time-dependent growth inhibition and apoptosis of Bel-7402 cells. It increased apoptosis through the up-regulation of Bax and the down-regulation of Bcl-2 in Bel-7402 cells. Moreover, celastrol induced the release of cytochrome c and increased the activation of caspase-3 and caspase-9, suggesting that celastrol-induced apoptosis was related to the mitochondrial pathway. These results indicated that celastrol could induce apoptosis in Bel-7402 cells, which may be associated with the activation of the mitochondria-mediated pathway.

scholarly journals The Short Isoform of DNAJB6 Protects against 1-Methyl-4-phenylpridinium Ion-Induced Apoptosis in LN18 Cells via Inhibiting Both ROS Formation and Mitochondrial Membrane Potential Loss

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yeon-Mi Hong ◽  
Yohan Hong ◽  
Yeong-Gon Choi ◽  
Sujung Yeo ◽  
Soo Hee Jin ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Mitochondrial Pathway ◽  
Caspase 9 ◽  
Ros Formation ◽  
Mitochondrial Membrane Potential Loss ◽  
Induced Apoptosis ◽  
Shock Proteins

In a previous study, we found that the short isoform of DNAJB6 (DNAJB6(S)) had been decreased in the striatum of a mouse model of Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). DNAJB6, one of the heat shock proteins, has been implicated in the pathogenesis of PD. In this study, we explored the cytoprotective effect of DNAJB6(S) against 1-methyl-4-phenylpyridinium ion- (MPP+-) induced apoptosis and the underlying molecular mechanisms in cultured LN18 cells from astrocytic tumors. We observed that MPP+ significantly reduced the cell viability and induced apoptosis in LN18 glioblastoma cells. DNAJB6(S) protected LN18 cells against MPP+-induced apoptosis not only by suppressing Bax cleavage but also by inhibiting a series of apoptotic events including loss of mitochondrial membrane potential, increase in intracellular reactive oxygen species, and activation of caspase-9. These observations suggest that the cytoprotective effects of DNAJB6(S) may be mediated, at least in part, by the mitochondrial pathway of apoptosis.

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 Rhein ElicitsIn VitroCytotoxicity in Primary Human Liver HL-7702 Cells by Inducing Apoptosis through Mitochondria-Mediated Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Guy-Armel Bounda ◽  
Wang Zhou ◽  
Dan-dan Wang ◽  
Feng Yu
Keyword(s):  
Cytochrome C ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Fatty Degeneration ◽  
Apoptotic Cells ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Induced Apoptosis

Objective. To study rhein-induced apoptosis signaling pathway and to investigate its molecular mechanisms in primary human hepatic cells.Results. Cell viability of HL-7702 cells treated with rhein showed significant decrease in dose-dependent manner. Following rhein treatment (25 μM, 50 μM, and 100 μM) for 12 h, the detection of apoptotic cells was significantly analyzed by flow cytometry and nuclear morphological changes by Hoechst 33258, respectively. Fatty degeneration studies showed upregulation level of the relevant hepatic markers (P< 0.01). Caspase activities expressed significant upregulation of caspase-3, caspase-9, and caspase-8. Moreover, apoptotic cells by rhein were significantly inhibited by Z-LEHD-FMK and Z-DEVD-FMK, caspase-9 inhibitor, and caspase-3 inhibitor, respectively. Overproduction of reactive oxygen species, lipid peroxidation, and loss of mitochondrial membrane potential were detected by fluorometry. Additionally, NAC, a ROS scavenger, significantly attenuated rhein-induced oxidative damage in HL-7702 cells. Furthermore, real-time qPCR results showed significant upregulation of p53, PUMA, Apaf-1, and Casp-9 and Casp-3 mRNA, with no significant changes of Fas and Cytochrome-c. Immunoblotting revealed significant Cytochrome-c release from mitochondria into cytosol and no change in Fas expression.Conclusion. Taken together, these observations suggested that rhein could induce apoptosis in HL-7702 cells via mitochondria-mediated signal pathway with involvement of oxidative stress mechanism.

scholarly journals Corn Silk (Zea mays L.) Induced Apoptosis in Human Breast Cancer (MCF-7) Cells via the ROS-Mediated Mitochondrial Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Mai M. Al-Oqail ◽  
Ebtesam S. Al-Sheddi ◽  
Nida N. Farshori ◽  
Shaza M. Al-Massarani ◽  
Eman A. Al-Turki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Caspase 3 ◽  
Mitochondrial Pathway ◽  
Ros Production ◽  
Human Breast ◽  
Caspase 9 ◽  
Corn Silk ◽  
Induced Apoptosis ◽  
Mcf 7

Cancer has been recognized as one of the life-threating diseases. Breast cancer is a leading cause of mortality among women. In spite of current developments in the therapy and diagnosis of cancer, the survival rate is still less. Recently, plant-derived natural products gain attention as anticancer agents due to the nontoxic nature. Therefore, the aim of present study was to investigate the anticancer capacity of corn silk extract (CSE) on human breast cancer (MCF-7) and normal human mesenchymal (hMSC-TERT4) cells. Following 24 h treatment to corn silk extract, the cytotoxicity was assessed by MTT, NRU, and morphological assays. The oxidative stress markers (GSH and LPO), ROS production, MMP change, and expression of apoptotic marker genes (p53, Bax, Bcl-2, caspase-3, and caspase-9) were also studied in MCF-7 cells treated at 250 to 1000 μg/ml of CSE for 24 h. Our results showed that CSE decreased the cell viability and increased the apoptosis in a dose-dependent manner. The level of LPO and ROS production was found significantly higher; however, GSH and MMP level was observed lower in CSE-treated MCF-7 cells. The real-time PCR data showed a significant upregulation in p53, Bax, caspase-3, and caspase-9 and downregulation in the mRNA expression of Bcl-2 genes in MCF-7 cells exposed to CSE. Collectively, the data from this study stated that corn silk extract induced apoptosis via the ROS-mediated mitochondrial pathway in MCF-7 cells.

scholarly journals Severibuxine, Isolated from Severinia buxifolia, Induces Apoptosis in HL-60 Leukemia Cells

2013 ◽  
Vol 8 (6) ◽  
pp. 1934578X1300800
Author(s):  
Chihiro Ito ◽  
Tomiyasu Murata ◽  
Midori Kato ◽  
Natsu Suzuki ◽  
Tian-Shung Wu ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Microscopic Analysis ◽  
Time Dependent ◽  
Root Bark ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Nuclear Condensation ◽  
Apoptotic Effect ◽  
Induced Apoptosis ◽  
Severinia Buxifolia

In an ongoing search for cancer-preventing compounds derived from plant sources, we isolated the quinolin-2,4-dione alkaloid severibuxine from the root bark of Severinia buxifolia collected in Taiwan and then examined the apoptotic effect of this compound. Severibuxine showed cytotoxicity to leukemia HL-60 cells (IC50 = 12.3±0.6 μM). Fluorescence microscopic analysis of cells stained with Hoechst 33342 indicated that the percentage of apoptotic cells showing nuclear condensation and fragmentation increased in a time-dependent manner. In addition, the activities of caspase-9 and caspase-3 were also enhanced in a time-dependent manner upon treatment with severibuxine. The addition of caspase-9 and caspase-3 inhibitors blocked severibuxine-mediated apoptosis. Upon treatment with severibuxine, the mitochondrial membrane potential decreased in a time-dependent manner. Severibuxine induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, which is triggered by mitochondrial dysfunction.

scholarly journals Delineation of the Molecular Mechanisms of Francisella tularensis-Induced Apoptosis in Murine Macrophages

2003 ◽  
Vol 71 (8) ◽  
pp. 4642-4646 ◽  
Author(s):  
Xin-He Lai ◽  
Anders Sjöstedt
Keyword(s):  
Francisella Tularensis ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Live Vaccine Strain ◽  
Intrinsic Apoptotic Pathway ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Murine Macrophages ◽  
Induced Apoptosis

ABSTRACT Francisella tularensis is a facultative intracellular bacterium capable of inducing apoptosis in murine macrophages. Here we analyzed the pathway leading to apoptosis in the murine macrophage-like cell line J774A.1 after infection with F. tularensis strain LVS (named LVS for live vaccine strain). We obtained evidence that the infection affected the mitochondria of the macrophages, since it induced release of the mitochondrial molecule cytochrome c into the cytosol and changed the potential over the mitochondrial membrane. Moreover, activation of caspase 9 and the executioner caspase 3 was also observed in the LVS-infected J774A.1 macrophages. The activated caspase 3 degraded poly(ADP-ribose) polymerase (PARP). All of these events were observed within 9 to 12 h after the initiation of infection, and maximum degradation of a synthetic caspase 3 substrate occurred at 18 h. The internucleosomal fragmentation and PARP degradation resulting from activation of this apoptotic pathway was prevented by the caspase 3 inhibitor Z-DEVD-fmk. No involvement of caspase 1, caspase 8, Bcl-2, or Bid was observed. Thus, the F. tularensis infection induces macrophage apoptosis through a pathway partly resembling the intrinsic apoptotic pathway.

scholarly journals Ailanthone Promotes Human Vestibular Schwannoma Cell Apoptosis and Autophagy by Downregulation of miR-21

2018 ◽  
Vol 26 (6) ◽  
pp. 941-948 ◽  
Author(s):  
Peizhen Yang ◽  
Dezhong Sun ◽  
Fei Jiang
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Ailanthus Altissima ◽  
Antitumor Activities ◽  
Caspase 9 ◽  
Chinese Medicinal Herb ◽  
Induced Apoptosis ◽  
Functional Actions

Ailanthone (AIL) is a quassinoid isolated from the traditional Chinese medicinal herb Ailanthus altissima. The antitumor activities of AIL have been reported in several cancers. The purpose of the present study was to explore the effect of AIL on vestibular schwannomas (VSs). Various concentrations of AIL (0‐1 μM) were used to treat human primary VS cells, and then cell viability, proliferation, apoptosis, and autophagy were assessed. Expression of miR-21 in VS cells was altered by miRNA transfection. The functional actions of AIL on miR-21 dysregulated cells were also assessed. AIL significantly reduced the viability of VS cells, and the IC50 value was 0.48 ± 0.023 μM. In response to 0.6 μM AIL, BrdU+ cell rate and cyclin D1 expression were reduced, apoptotic cell rate was increased, caspase 3 and caspase 9 were cleaved, Beclin-1 and LC3-II were accumulated, and p62 was downregulated. miR-21 was lowly expressed in AIL-treated cells, and AIL-induced apoptosis and autophagy were attenuated by miR-21 overexpression. In addition, AIL downregulated Ras and Raf and deactivated MEK, ERK, mTOR, and p70S6K, while the downregulation and deactivation induced by AIL were reversed by miR-21 overexpression. To conclude, AIL inhibited VS cell proliferation and induced apoptosis and autophagy. The antitumor activities of AIL in VS cells were realized possibly via downregulation of miR-21 and blocking the Ras/Raf/MEK/ERK and mTOR pathways.

scholarly journals Leptospira interrogans Induces Apoptosis in Macrophages via Caspase-8- and Caspase-3-Dependent Pathways

2008 ◽  
Vol 77 (2) ◽  
pp. 799-809 ◽  
Author(s):  
Dandan Jin ◽  
David M. Ojcius ◽  
Dexter Sun ◽  
Haiyan Dong ◽  
Yihui Luo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Host Cells ◽  
Caspase 8 ◽  
Lamin A ◽  
Leptospira Interrogans ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Caspase 6 ◽  
Induced Apoptosis

ABSTRACT Apoptosis of host cells plays an important role in modulating the pathogenesis of many infectious diseases. It has been reported that Leptospira interrogans, the causal agent of leptospirosis, induces apoptosis in macrophages and hepatocytes. However, the molecular mechanisms responsible for host cell death remained largely unknown. Here we demonstrate that L. interrogans induced apoptosis in a macrophage-like cell line, J774A.1, and primary murine macrophages in a time- and dose-dependent manner. Apoptosis was associated with the activation of cysteine aspartic acid-specific proteases (caspase-3, caspase-6, and caspase-8), the increased expression of Fas-associated death domain (FADD), and the cleavage of the caspase substrates poly(ADP-ribose) polymerase (PARP) and nuclear lamina protein (lamin A and lamin C). Caspase-9 was activated to a lesser extent, whereas no release of cytochrome c from mitochondria was detectable. Inhibition of caspase-8 impaired L. interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, suggesting that apoptosis is initiated via caspase-8 activation. Furthermore, caspase-3 was required for the activation of caspase-6 and seemed to be involved in caspase-9 activation through a feedback amplification loop. These data indicate that L. interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADD-caspase-8-dependent pathway, independently of mitochondrial cytochrome c-caspase-9-dependent signaling.

Synergistic Antitumor Effect of 5-Fluorouracil Combined with Constituents from Pleurospermum lindleyanum in Hepatocellular carcinoma SMMC-7721 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiao-Feng Zhu ◽  
Xiao-Jin Li ◽  
Zhong-Lian Cao ◽  
Xiu-Jie Liu ◽  
Ping Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Effectiveness ◽  
Synergistic Effects ◽  
Folk Medicine ◽  
Inhibitory Effect ◽  
Caspase 9 ◽  
Whole Plant ◽  
Anti Cancer ◽  
Induced Apoptosis

Background: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells. Objective: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with 5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms. Methods: Sequential chromatographic techniques were conducted for the isolation studies. The isolates structures were established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western blot were used to examine apoptosis and protein expression. Results: A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P. lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote 5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP. Conclusion: Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular carcinoma cells.

The Anti-Proliferative Activity of Anisosciadone: A New Guaiane Sesquiterpene from Anisosciadium lanatum

2019 ◽  
Vol 19 (9) ◽  
pp. 1114-1119 ◽  
Author(s):  
Ahmed A. Mahmoud ◽  
Wael M. El-Sayed
Keyword(s):  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Chemical Constituents ◽  
Spectroscopic Techniques ◽  
Significant Activity ◽  
Caspase 9 ◽  
P53 Expression ◽  
Expression And Activity

Background: The increase in cancer rate and the development of resistant tumors require a continuous search for new anticancer agents. Aims: This study aimed to analyze and identify the chemical constituents of Anisosciadium lanatum, and to investigate the antiproliferative activity of the identified constituents against various human cell lines (HepG2, MCF7, HT29, A549, and PC3) along with the possible molecular mechanisms involved. Methods: The structure of the isolated compounds was determined by spectroscopic techniques including HRFABMS, GC-MS, IR, and 400 MHz 1D and 2D NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY). The antiproliferative activity and IC50 value of the isolated compounds were measured and compared to doxorubicin. Results: A new guaiane sesquiterpene containing a rare epoxide structural element, 10β,11β−epoxy−1α,4β,5β,7αΗ- guaiane-9-one, anisosciadone (1), and stigmasterol (2) have been isolated from the plant. Anisosciadone (1) showed a significant antiproliferative activity against liver, colon, and lung cells only, while stigmasterol (2) had a significant activity against liver, colon, and breast cells. Both 1 and 2 caused no cytotoxicity to normal fibroblasts. Anisosciadone elevated the expression and activity of Caspase 3 as well as p53 expression without affecting Caspase 9 in HepG2 cells. It also caused ~ 50% downregulation in cdk1 expression. Conclusion: Taken together, anisosciadone was specific in action against cancer cells and induced apoptosis in liver cells. It also has a unique feature by elevating the expression and activity of Caspase 3 without affecting the initiator Caspase 9. Therefore, anisosciadone deserves more investigation as a targeted therapy for cancer.

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