21-benzylidene digoxin decreases proliferation by inhibiting the egfr/erk signaling pathway and induces apoptosis in hela cells

Publication date: Available online 6 December 2019Source: SteroidsAuthor(s): Marco Túlio C. Pessôa, Jéssica M.M. Valadares, Sayonarah C. Rocha, Simone C. Silva, Jeff P. McDermott, Gladis Sánchez, Fernando P. Varotti, Cristóforo Scavone, Rosy I.M.A. Ribeiro, José A.F.P. Villar, Gustavo Blanco, Leandro A. BarbosaAbstractCardiotonic steroids (CTS) are agents traditionally known for their capacity to bind to the Na,K-ATPase (NKA), affecting the ion transport and the contraction of the heart. Natural CTS have been shown to also have effects on cell signaling pathways. With the goal of developing a new CTS derivative , we synthesized a new digoxin derivative, 21-benzylidene digoxin (21-BD). Previously, we have shown that this compound binds to NKA and has cytotoxic actions on cancer, but not on normal cells. Here, we further studied the mechanisms of actions of 21-BD. Working with HeLa cells, we found that 21-BD decreases the basal, as well as the insulin stimulated proliferation. 21-BD reduces phosphorylation of the epidermal growth factor receptor (EGFR) and extracellular-regulated kinase (ERK), which are involved in pathways that stimulate cell proliferation. In addition, 21-BD promotes apoptosis, which is mediated by the translocation of Bax from the cytosol to mitochondria and the release of mitochondrial cytochrome c to the cytosol. 21-BD also activated caspases-8, -9 and -3, and induced the cleavage of poly (ADP-ribose) polymerase-1 (...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research

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Conclusion: ATLIII has shown significant efficacy to inhibit IFN-γ-triggered Jak3/Stat3 pathway-dependent IDO activation, and do so through a direct binding to Jak3 protein. This study elucidated a new mechanism for the anticancer effect of ATLIII, which may provide a feasible target for the clinical immunotherapy of malignant tumors.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study aims to examine the anti-inflammatory effects and potential molecular mechanism of GH, and provide new insights toward the treatment of inflammation. GH inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production, and messenger RNA (mRNA) expression to attenuate inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells or stimulated bone marrow-derived macrophages (BMDMs). GH inhibited nuclear factor-κB (NF-κB) and mitogen-activated prot...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 15 January 2020Source: Life SciencesAuthor(s): Zhi Zeng, Zi-yao Wang, Yu-kun Li, Dong-mei Ye, Juan Zeng, Jia-li Hu, Pi-feng Chen, Jiao Xiao, Juan Zou, Zhen-hua LiAbstractNuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that can regulate downstream target gene expression. Kelch-like ECH-associated protein 1 (Keap1) negatively regulates Nrf2 activation and translocation to target its 26S proteasomal degradation. It has been widely reported that the Keap1/Nrf2 pathway is associated with tumorigenesis, chemotherapy resistance and progression and development...
Source: Life Sciences - Category: Biology Source Type: research
ConclusionsOverall, our results suggest that KRG exerts an anti-inflammatory effect on BPA-treated A549 cells via the suppression of ROS and down-regulation of NF-κB activation and COX-2 expression which leads to a decrease in cellular migration and MMP-9 expression. These results provide a new possible therapeutic application of KRG to protect BPA-induced possible inflammatory disorders.Graphical abstract
Source: Journal of Ginseng Research - Category: Complementary Medicine Source Type: research
The objective of this study was to investigate the effects and molecular mechanism of casticin on DNA damage and repair in human lung cancer A549 cells. Cell viability was determined by flow cytometric assay. The DNA damage was evaluated by 4’,6-diamidino-2-phenylindole (DAPI) staining and electrophoresis which included comet assay and DNA gel electrophoresis. The protein levels associated with DNA damage and repair were analyzed by western blotting. The expression and translocation of p-H2A.X were observed by confocal laser microscopy. Casticin reduced total viable cell number and induced DNA condensation, fragm...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Conclusion: The plasma 16S rDNA levels increased in patients with PCa who have biochemical recurrence and 16S rDNA levels were higher in patients with higher-grade PCa.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study, therefore, introduces a novel approach to combating TNBC by targeting the FABP/EET/CYP-associated metastatic signaling network.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we showed that knockdown of SIRT6 or PARP1 gene expression significantly inhibited HMGB1 cytoplasmic translocation and autophagy. Meanwhile, we found that SIRT6, an important upstream protein of PARP1, associated with PARP1, leading to the stimulation of polyADP-ribose polymerase activity. We further demonstrated that SIRT6 and PARP1 activation were required for chemotherapy-induced ADP-ribosylation of HMGB1 in leukemic cells and then influenced the acetylation of HMGB1, finally promoting the autophagy of leukemic cells mediated by HMGB1 translocation. These findings provide new insights into the mechanism o...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
Conclusion: In this patient cohort, pazopanib was associated with inferior OS in comparison with sunitinib for metastatic nccRCC. Larger trials are ideally warranted to confirm these results. PMID: 31921344 [PubMed]
Source: Ecancermedicalscience - Category: Cancer & Oncology Tags: Ecancermedicalscience Source Type: research
Silencing of PPM1D inhibits cell proliferation and invasion through the p38 MAPK and p53 signaling pathway in papillary thyroid carcinoma. Oncol Rep. 2020 Jan 09;: Authors: Lu ZW, Wen D, Wei WJ, Han LT, Xiang J, Wang YL, Wang Y, Liao T, Ji QH Abstract Endeavors towards identifying key molecular markers for early diagnosis and treatment are driving the clinical study of papillary thyroid carcinoma (PTC). Recent studies have indicated that protein phosphatase, Mg2+/Mn2+ dependent, 1D (PPM1D) exerts an oncogenic function by increasing cell proliferation, migration and invasion in various cancer ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
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