scholarly journals Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells

2021 ◽  
Vol 22 (24) ◽  
pp. 13462
Author(s):  
Irene Rodríguez ◽  
Ester Saavedra ◽  
Henoc del Rosario ◽  
Juan Perdomo ◽  
José Quintana ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Human Melanoma ◽  
Mitogen Activated Protein Kinase ◽  
World Health ◽  
Cytochrome C Release ◽  
Mitogen Activated Protein ◽  
Apoptosis Pathways ◽  
Apoptotic Pathways ◽  
Health Organization

The World Health Organization reported that approximately 324,000 new cases of melanoma skin cancer were diagnosed worldwide in 2020. The incidence of melanoma has been increasing over the past decades. Targeting apoptotic pathways is a potential therapeutic strategy in the transition to preclinical models and clinical trials. Some naturally occurring products and synthetic derivatives are apoptosis inducers and may represent a realistic option in the fight against the disease. Thus, chalcones have received considerable attention due to their potential cytotoxicity against cancer cells. We have previously reported a chalcone containing an indole and a pyridine heterocyclic rings and an α-bromoacryloylamido radical which displays potent antiproliferative activity against several tumor cell lines. In this study, we report that this chalcone is a potent apoptotic inducer for human melanoma cell lines SK-MEL-1 and MEL-HO. Cell death was associated with mitochondrial cytochrome c release and poly(ADP-ribose) polymerase cleavage and was prevented by a non-specific caspase inhibitor. Using SK-MEL-1 as a model, we found that the mechanism of cell death involves (i) the generation of reactive oxygen species, (ii) activation of the extrinsic and intrinsic apoptotic and mitogen-activated protein kinase pathways, (iii) upregulation of TRAIL, DR4 and DR5, (iv) downregulation of p21Cip1/WAF1 and, inhibition of the NF-κB pathway.

scholarly journals Multiple Targets of 3-Dehydroxyceanothetric Acid 2-Methyl Ester to Protect Against Cisplatin-Induced Cytotoxicity in Kidney Epithelial LLC-PK1 Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 878 ◽  
Author(s):  
Dahae Lee ◽  
Ki Hyun Kim ◽  
Won Yung Lee ◽  
Chang-Eop Kim ◽  
Sang Hyun Sung ◽  
...  
Keyword(s):  
Cell Death ◽  
Methyl Ester ◽  
Mapk Pathway ◽  
Apoptotic Cell ◽  
B Cell Lymphoma ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Targets ◽  
Mitogen Activated Protein ◽  
Apoptosis Pathways

Chronic exposure to cisplatin, a potent anticancer drug, causes irreversible kidney damage. In this study, we investigated the protective effect and mechanism of nine lupane- and ceanothane-type triterpenoids isolated from jujube (Ziziphus jujuba Mill., Rhamnaceae) on cisplatin-induced damage to kidney epithelial LLC-PK1 cells via mitogen-activated protein kinase (MAPK) and apoptosis pathways. Cisplatin-induced LLC-PK1 cell death was most significantly reduced following treatment with 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME). Additionally, apoptotic cell death was significantly reduced. Expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 was markedly suppressed by 3DC2ME, indicating inhibition of the MAPK pathway. Treatment with 3DC2ME also significantly reduced expression of active caspase-8 and -3, Bcl-2-associated X protein (Bax), and B cell lymphoma 2 (Bcl-2), indicating the inhibition of apoptosis pathways in the kidneys. We also applied the network pharmacological analysis and identified multiple targets of 3DC2ME related to MAPK signaling pathway and apoptosis.

scholarly journals Implication of p38 mitogen-activated protein kinase isoforms (α, β, γ and δ) in CD4+ T-cell infection with human immunodeficiency virus type I

2008 ◽  
Vol 89 (7) ◽  
pp. 1661-1671 ◽  
Author(s):  
Dolores Gutierrez-Sanmartin ◽  
Eduardo Varela-Ledo ◽  
Antonio Aguilera ◽  
Susana Romero-Yuste ◽  
Patricia Romero-Jung ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Death ◽  
T Cell ◽  
Protein Kinase ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Mitogen Activated Protein Kinase ◽  
Immunodeficiency Virus ◽  
Mitogen Activated Protein ◽  
Hiv 1

The CD4+ T-cell reduction characteristic of human immunodeficiency virus type 1 (HIV-1) infection is thought to result, in addition to infected T-cell death, mainly from uninfected bystander T-cell apoptosis. Nevertheless, the immunological and virological mechanisms leading to T-cell death during HIV-1 infection are not yet fully understood. In the present study, we analysed the individual implication of the p38 mitogen-activated protein kinase (MAPK) isoforms (p38α, p38β, p38γ and p38δ) during apoptosis induced by HIV-1, taking into account that HIV-1 replication is known to be blocked by p38 inhibitors. For this purpose, we used the SupT1 cell line, where death induced by HIV-1 mainly occurs by uninfected bystander cell apoptosis. A variety of SupT1-based cell lines were constructed constitutively expressing, under the control of cytomegalovirus promoter (PCMV), each dominant-negative (dn) p38 isoform and each wild-type p38 isoform as a control. An enhanced green fluorescent protein marker gene, under the control of the HIV-1 promoter, was inserted in all of them. These cell lines were infected with HIV-1 and analysed by flow cytometry. We found that survival in SupT1-based cell lines infected by HIV-1 was increased by the p38αdn, p38γdn and p38δdn isoforms, but not by the p38βdn isoform. HIV-1 replication was delayed most by p38δdn and to a lesser extent by p38αdn and p38γdn. Moreover, these three isoforms, p38αdn, p38γdn and p38δdn, reduced apoptosis induced by HIV-1. These results suggest that, in SupT1-based cell lines, p38α, p38γ and p38δ, but not p38β, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells.

Response to Austriaco on Vaccine Passports

2021 ◽  
Vol 46 (4) ◽  
pp. 4-4
Author(s):  
Joseph Meaney ◽  
Keyword(s):  
World Health Organization ◽  
Cell Lines ◽  
Yellow Fever ◽  
International Travel ◽  
World Health ◽  
Yellow Fever Vaccine ◽  
Work Activities ◽  
The World ◽  
Health Organization

This essay clarifies the author’s objections to COVID-19 vaccine credentials voiced in “The Ethics of COVID-19 Vaccine Passports.” The author’s objections centered on discriminatory practices based on vaccine status for domestic social and work activities, but he agrees with the World Health Organization that these credentials should not be required for international travel. In addition, there is a significant ethical different between currently available COVID-19 vaccines and the yellow fever vaccine because the former are produced or tested using abortion-derived cell lines. The yellow fever vaccine is much less ethically problematic. This situation could change with the approval of new COVID-19 vaccines without links to abortion-derived cell lines.

scholarly journals MAP Kinase OsMEK2 and OsMPK1 Signaling for Ferroptotic Cell Death in Rice-Magnaporthe oryzae Interactions

2020 ◽  
Author(s):  
Sarmina Dangol ◽  
Raksha Singh ◽  
Khoa Nam Nguyen ◽  
Yafei Chen ◽  
Juan Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Map Kinase ◽  
Signaling Pathways ◽  
Magnaporthe Oryzae ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Microbial Pathogens ◽  
Blast Disease ◽  
Related Cell ◽  
Mitogen Activated Protein

ABSTRACTMitogen-activated protein kinase (MAPK) signaling is required for plant cell death responses to invading microbial pathogens. Ferric ions and reactive oxygen species (ROS) accumulate in rice (Oryza sativa) tissues undergoing cell death during Magnaporthe oryzae infection. Here, we report that rice MAP kinase (OsMEK2 and OsMPK1) signaling cascades are involved in iron- and ROS-dependent ferroptotic cell death responses of rice to M. oryzae infection. OsMEK2 interacted with OsMPK1 in the cytoplasm, and OsMPK1 moved from the cytoplasm into the nucleus to bind to the OsWRKY90 transcription factor. OsMEK2 expression may trigger OsMPK1-OsWRKY90 signaling pathways in the nucleus. Avirulent M. oryzae infection in ΔOsmek2 mutant rice did not trigger iron and ROS accumulation and lipid peroxidation, and also downregulated OsMPK1, OsWRKY90, OsRbohB, and OsPR-1b expression. However, OsMEK2 overexpression induced ROS-and iron-dependent cell death in rice during M. oryzae infection. The downstream MAP kinase (OsMPK1) overexpression induced ROS- and iron-dependent ferroptotic cell death in the compatible rice-M. oryzae interaction. These data suggest that the OsMEK2-OsMPK1-OsWRKY90 signaling cascade is involved in the ferroptotic cell death in rice. The small-molecule inducer erastin triggered iron- and lipid ROS-dependent, but OsMEK2-independent, ferroptotic cell death in ΔOsmek2 mutant plants during M. oryzae infection. Disease-related cell death was lipid ROS-dependent and iron-independent in the ΔOsmek2 mutant plants. These combined results suggest that OsMEK2 and OsMPK1 expression positively regulates iron- and ROS-dependent ferroptotic cell death via OsMEK2-OsMPK1-OsWRKY90 signaling pathways, and blast disease (susceptibility)-related cell death was ROS-dependent but iron-independent in rice-M. oryzae interactions.

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