scholarly journals Extrinsic or Intrinsic Apoptosis by Curcumin and Light: Still a Mystery

2019 ◽  
Vol 20 (4) ◽  
pp. 905 ◽  
Author(s):  
Vesselina Laubach ◽  
Roland Kaufmann ◽  
August Bernd ◽  
Stefan Kippenberger ◽  
Nadja Zöller
Keyword(s):  
Cell Lines ◽  
Curcuma Longa ◽  
Death Receptor ◽  
Redox Balance ◽  
Death Receptors ◽  
Test System ◽  
Tnf Α ◽  
Epithelial Cell Lines ◽  
Membrane Bound ◽  
Apoptotic Effects

Curcumin—a rhizomal phytochemical from the plant Curcuma longa—is well known to inhibit cell proliferation and to induce apoptosis in a broad range of cell lines. In previous studies we showed that combining low curcumin concentrations and subsequent ultraviolet A radiation (UVA) or VIS irradiation induced anti-proliferative and pro-apoptotic effects. There is still debate whether curcumin induces apoptosis via the extrinsic or the intrinsic pathway. To address this question, we investigated in three epithelial cell lines (HaCaT, A431, A549) whether the death receptors CD95, tumor necrosis factor (TNF)-receptor I and II are involved in apoptosis induced by light and curcumin. Cells were incubated with 0.25–0.5 µg/mL curcumin followed by irradiation with 1 J/cm2 UVA. This treatment was combined with inhibitors specific for distinct membrane-bound death receptors. After 24 h apoptosis induction was monitored by quantitative determination of cytoplasmic histone-associated-DNA-fragments. Validation of our test system showed that apoptosis induced by CH11 and TNF-α could be completely inhibited by their respective antagonists. Interestingly, apoptosis induced by curcumin/light treatment was reversed by none of the herein examined death receptor antagonists. These results indicate a mechanism of action independent from classical death receptors speaking for intrinsic activation of apoptosis. It could be speculated that a shift in cellular redox balance might prompt the pro-apoptotic processes.

scholarly journals Dynamics of RASSF1A/MOAP-1 Association with Death Receptors

2008 ◽  
Vol 28 (14) ◽  
pp. 4520-4535 ◽  
Author(s):  
Caitlin J. Foley ◽  
Holly Freedman ◽  
Sheryl L. Choo ◽  
Christina Onyskiw ◽  
Nai Yang Fu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor Receptor ◽  
Death Receptor ◽  
Death Receptors ◽  
Tumor Formation ◽  
Receptor Interaction ◽  
Binding Motif ◽  
Death Domain ◽  
Interacting Protein ◽  
Receptor Complexes ◽  
Tnf Α

ABSTRACT RASSF1A is a tumor suppressor protein involved in death receptor-dependent apoptosis utilizing the Bax-interacting protein MOAP-1 (previously referred to as MAP-1). However, the dynamics of death receptor recruitment of RASSF1A and MOAP-1 are still not understood. We have now detailed recruitment to death receptors (tumor necrosis factor receptor 1 [TNF-R1] and TRAIL-R1/DR4) and identified domains of RASSF1A and MOAP-1 that are required for death receptor interaction. Upon TNF-α stimulation, the C-terminal region of MOAP-1 associated with the death domain of TNF-R1; subsequently, RASSF1A was recruited to MOAP-1/TNF-R1 complexes. Prior to recruitment to TNF-R1/MOAP-1 complexes, RASSF1A homodimerization was lost. RASSF1A associated with the TNF-R1/MOAP-1 or TRAIL-R1/MOAP-1 complex via its N-terminal cysteine-rich (C1) domain containing a potential zinc finger binding motif. Importantly, TNF-R1 association domains on both MOAP-1 and RASSF1A were essential for death receptor-dependent apoptosis. The association of RASSF1A and MOAP-1 with death receptors involves an ordered recruitment to receptor complexes to promote cell death and inhibit tumor formation.

scholarly journals Death Receptors DR4 and DR5 Undergo Spontaneous and Ligand-Mediated Endocytosis and Recycling Regardless of the Sensitivity of Cancer Cells to TRAIL

2021 ◽  
Vol 9 ◽  
Author(s):  
Artem A. Artykov ◽  
Anne V. Yagolovich ◽  
Dmitry A. Dolgikh ◽  
Mikhail P. Kirpichnikov ◽  
Daria B. Trushina ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Lines ◽  
Death Receptor ◽  
Brefeldin A ◽  
Death Receptors ◽  
Resistant Cell ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Receptor Endocytosis ◽  
Trail Signaling

Tumor necrosis factor-associated ligand inducing apoptosis (TRAIL) induces apoptosis through the death receptors (DRs) 4 and 5 expressed on the cell surface. Upon ligand stimulation, death receptors are rapidly internalized through clathrin-dependent and -independent mechanisms. However, there have been conflicting data on the role of death receptor endocytosis in apoptotic TRAIL signaling and possible cell type-specific differences in TRAIL signaling have been proposed. Here we have compared the kinetics of TRAIL-mediated internalization and subsequent recycling of DR4 and DR5 in resistant (HT-29 and A549) and sensitive (HCT116 and Jurkat) tumor cell lines of various origin. TRAIL stimulated the internalization of both receptors in a concentration-dependent manner with similar kinetics in sensitive and resistant cell lines without affecting the steady-state expression of DR4 and DR5 in cell lysates. Using the receptor-selective TRAIL variant DR5-B, we have shown that DR5 is internalized independently of DR4 receptor. After internalization and elimination of TRAIL from culture medium, the receptors slowly return to the plasma membrane. Within 4 h in resistant or 6 h in sensitive cells, the surface expression of receptors was completely restored. Recovery of receptors occurred both from newly synthesized molecules or from trans-Golgi network, as cycloheximide and brefeldin A inhibited this process. These agents also suppressed the expression of cell surface receptors in a time- and concentration-dependent manner, indicating that DRs undergo constitutive endocytosis. Inhibition of receptor endocytosis by sucrose led to sensitization of resistant cells to TRAIL and to an increase in its cytotoxic activity against sensitive cells. Our results confirm the universal nature of TRAIL-induced death receptor endocytosis, thus cell sensitivity to TRAIL can be associated with post-endocytic events.

The Effect of IL-26 on TNF-α-Induced CXCL8 Responses by Colonic Epithelial Cell Lines

2019 ◽  
Vol 48 (8) ◽  
pp. 822-834
Author(s):  
Isabelle M. Weishaar ◽  
Rebecca S. Young ◽  
Brody M. Wiles ◽  
Dennis W. McGee
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Colonic Epithelial Cell ◽  
Tnf Α ◽  
Epithelial Cell Lines

scholarly journals Exploring cardioprotective potential of esculetin against isoproterenol induced myocardial toxicity in rats: in vivo and in vitro evidence

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chitikela P. Pullaiah ◽  
Vinod K. Nelson ◽  
Sushma Rayapu ◽  
Narasimha Kumar G V ◽  
Thyagaraju Kedam
Keyword(s):  
Body Weight ◽  
Cell Lines ◽  
Lysosomal Enzymes ◽  
H9c2 Cell ◽  
Rna Expression ◽  
Cell Necrosis ◽  
Tnf Α ◽  
Intracellular Ros ◽  
Membrane Bound

Abstract Background Esculetin is a natural coumarin derivative from various plants with multiple pharmacological effects. Hence, the present study was undertaken to explore the cardio protective potential of esculetin against isoproterenol induced myocardial toxicity in rats. Methods The treatment schedule was fixed for 28 days and the rats were divided into five groups of six each. Rats of group I received the normal saline and served as normal control, group II was received ISO (100 mg/kg body weight) for last two consecutive days of the study and served as disease control. Groups III and IV received esculetin 10 and 20 mg/kg body weight respectively once a day per oral for 28 days along with ISO for last two consecutive days of the study. Cardiac biomarkers such as CK-MB and LDH, membrane bound Na+ /K+ ATPases activity, myocardial lysosomal enzymes activity and tissue antioxidants status were estimated in the heart tissue samples. The histopathological changes in the myocardium were also assessed. Further, DPPH assay was done to evaluate the free radicals scavenging potential of esculetin. Cytoxicity assay, intracellular ROS levels by DCFDA assay and m-RNA expression of TNF-α, IL-6 and NF-κB by quantitative RT-PCR in H9c2 cell lines. Results The increased levels of CK-MB, LDH, LPO, myocardial lysosomal enzymes and membrane bound Na+ /K+ ATPase levels by ISO administration was significantly increased with concomitant decrease in tissue antioxidant enzymes such as GSH, Catalase, and SOD. Pre-treatment with esculetin for 28 days has significantly decreased the levels of cardiac bio-markers, lysosomal enzymes, membrane bound Na+ /K+ ATPase levels as well as Lipid peroxides which is in contrary to the ISO group. Amelioration of the antioxidant levels were also found in esculetin treated groups. Histopathological examination of heart reveals that myocardial degeneration, mononuclear cell infiltration was noticed in ISO treated rats, whereas the same was restored with esculetin treatment. In H9C2 cell lines esculetin could effectively reduced intracellular ROS inhibition and m-RNA expression of pro-inflammatory cytokines including TNF-α, IL-6 and NF-κB to prevent apoptosis or cell necrosis. Conclusion The study provides the evidence of cardioprotective potentials of esculetin against isoproterenol induced myocardial infarction by antioxidant and myocardial membrane stabilization along with in vitro protection from arsenic induced ROS cell necrosis or apoptosis in H9C2 cells.

scholarly journals The hepatoprotective effect of Cheral as anti-oxidant and anti-inflammation on mice (Mus musculus) with breast cancer

2020 ◽  
Vol 9 (2) ◽  
pp. 153-160
Author(s):  
Feri Eko Hermanto ◽  
Aris Soewondo ◽  
Hideo Tsuboi ◽  
Mansur Ibrahim ◽  
Muhaimin Rifa'i
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Curcuma Longa ◽  
Redox Balance ◽  
Related Factor ◽  
Mice Model ◽  
Cancer Group ◽  
Tnf Α ◽  
Ifn Γ

Introduction: Recent studies have reported that breast cancer may affect the physiology of other organs, including oxidative stress in the liver. On the other hand, some agents such as white turmeric (Curcuma longa) and Meniran (Phyllanthus niruri) seem to maintain redox stability and immunomodulation. Both of them are combined into Cheral potion. This study was aimed to investigate the Cheral efficacy in modulating oxidative stress based on Nuclear factor erythroid 2-related factor 2 (Nrf2), HEME OXIGenase (HO), and superoxide dismutase (SOD) levels as well as pro-inflammatory cytokines under breast cancer condition in vivo. Methods: Nrf2, HO, and SOD from hepatocytes, and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) from splenocytes were measured by flow cytometry after 14 days of Cheral administration. Results: The results showed that mice model for breast cancer underwent oxidative stress denoted by high levels of HO, and SOD accompanied by increased levels of TNF-α and IFN-γ in the cancer group compared to normal healthy group (P<0.05). In contrast, Cheral treatment was able to modulate redox balance by declining levels of HO, SOD, TNF-α, and IFN-γ, but not Nrf2, compared to cancer group (P<0.05). Conclusion: The results showed that breast cancer could alter the host’s physiology, including liver oxidative stress. The levels of TNF-α and IFN-γ might contribute to regulation of redox balance in the liver. However, Cheral has potency as an alternative therapeutic agent to reduce oxidative stress in the liver under breast cancer condition.

scholarly journals Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1β, TNF-α and LPS

1996 ◽  
Vol 9 (10) ◽  
pp. 2036-2043 ◽  
Author(s):  
M.M. Verheggen ◽  
P.Th.W. van Hal ◽  
P.W.C. Adriaansen-Soeting ◽  
B.J.A. Goense ◽  
H.C. Hoogsteden ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Glucocorticoid Receptor ◽  
Cell Lines ◽  
Bronchial Epithelial Cell ◽  
Receptor Expression ◽  
Human Bronchial Epithelial Cell ◽  
Bronchial Epithelial ◽  
Tnf Α ◽  
Epithelial Cell Lines

scholarly journals Direct Repression of FLIP Expression by c-myc Is a Major Determinant of TRAIL Sensitivity

2004 ◽  
Vol 24 (19) ◽  
pp. 8541-8555 ◽  
Author(s):  
M. Stacey Ricci ◽  
Zhaoyu Jin ◽  
Michael Dews ◽  
Duonan Yu ◽  
Andrei Thomas-Tikhonenko ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Tumor Cell ◽  
Cell Lines ◽  
Death Receptor ◽  
Major Determinant ◽  
Luciferase Reporter ◽  
Tnf Α ◽  
Significant Difference ◽  
Trail Sensitivity ◽  
Resistant Cells

ABSTRACT Tumor necrosis factor alpha (TNF-α)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF-α family of death receptor ligands and holds great therapeutic potential as a tumor cell-specific cytotoxic agent. Using a panel of established tumor cell lines and normal cells, we found a significant difference between the number of TRAIL-sensitive cells expressing high levels of c-myc and TRAIL-resistant cells expressing low levels of c-myc (P < 0.05, n = 19). We also found a direct linear correlation between c-myc levels and TRAIL sensitivity in TRAIL-sensitive cell lines (r = 0.94, n = 6). Overexpression of c-myc or activation of a myc-estrogen receptor (ER) fusion sensitized TRAIL-resistant cells to TRAIL. Conversely, small interfering RNA (siRNA)-mediated knockdown of c-myc significantly reduced both c-myc expression and TRAIL-induced apoptosis. The gene encoding the inhibitor of caspase activation, FLICE inhibitory protein (FLIP), appears to be a direct target of c-myc-mediated transcriptional repression. Overexpression of c-myc or activation of myc-estrogen receptor (ER) decreased FLIP levels both in cell culture and in mouse models of c-myc-induced tumorigenesis, while knocking down c-myc using siRNA increased FLIP expression. Chromatin immunoprecipitation and luciferase reporter analyses showed that c-myc binds and represses the human FLIP promoter. c-myc expression enhanced TRAIL-induced caspase 8 cleavage and FLIP cleavage at the death-inducing signaling complex. Combined siRNA-mediated knockdown of FLIP and c-myc resensitized cells to TRAIL. Therefore, c-myc down-regulation of FLIP expression provides a universal mechanism to explain the ability of c-myc to sensitize cells to death receptor stimuli. In addition, identification of c-myc as a major determinant of TRAIL sensitivity provides a potentially important screening tool for identification of TRAIL-sensitive tumors.

scholarly journals IL-22 Enhances TNF-α- and IL-1-Induced CXCL8 Responses by Intestinal Epithelial Cell Lines

Inflammation ◽  
2017 ◽  
Vol 40 (5) ◽  
pp. 1726-1734 ◽  
Author(s):  
Rebecca S. Young ◽  
Brody M. Wiles ◽  
Dennis W. McGee
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Tnf Α ◽  
Epithelial Cell Lines
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