Anticancer effects of ginsenoside Rk3 on non-small cell lung cancer cells: in vitro and in vivo

2017 ◽  
Vol 8 (10) ◽  
pp. 3723-3736 ◽  
Author(s):  
Zhiguang Duan ◽  
Jianjun Deng ◽  
Yangfang Dong ◽  
Chenhui Zhu ◽  
Weina Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Death Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anticancer Effects ◽  
Induced Apoptosis

Ginsenoside-Rk3 inhibited proliferation, arrested the cell cycle, induced apoptosisviadeath receptor-mediated mitochondria-dependent pathways and suppressed angiogenesis and tumor growth.

A pilot study on the anticancer effects of novel candidate agent COH-SR4 in lung cancer.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 28-28
Author(s):  
David Berz
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anticancer Effects ◽  
Resected Tumor

28 Background: Non-small cell lung cancer is the leading cause of cancer deaths in the US. The success of current treatment strategies is limited by frequent aberrations in multiple signaling pathways. This includes loss-of-function mutations in the tumor suppressor p53 and activating mutations in multiple growth factor receptors, which converge to activate PI3K/Akt pathway. This calls for the development of novel, more active treatments. We investigated the anti-cancer effects of a novel compound called 1, 3 bis (3, 5-dichlorophenyl) urea (COH-SR4) in lung cancer. Methods: The anticancer effects of COH-SR4 were tested in p53-null H358 lung cancer cells. The antiproliferative effects were investigated in vitro by MTT assay. The bio-availability and antitumor effects were determined in vivo following the administration of 4 mg/kg of COH-SR4 to mice and H358-nu/nu nude mice xenografts. Results: The treatment with COH-SR4 resulted in effective inhibition of the proliferative potential of H358 lung cancer cells [IC50: 23+2 µM], effectively inducing apoptosis. The 4 mg/kg COH-SR4 administration resulted in a free serum concentration of 1+ 0.3 µM. Regression of established H358-xenografts was achieved without any overt toxicity. The histopathology of resected tumor sections revealed an increase in pAMPK (T172) and a decrease in the nuclear proliferative marker Ki 67 and angiogenesis marker CD31. Western blot analyses of resected tumor lysates revealed a decrease in pAkt (S473) and anti-apoptotic protein Bcl2 along with an increase in pAMPK (T172), pro-apoptotic Bax and cleaved PARP levels. In addition, COH-SR4 lead to a decrease in the levels of the cell cycle regulators CDK4 and cyclin B1 as well as the mesenchymal marker vimentin, whilst increasing the epithelial marker E-cadherin. Conclusions: COH-SR4 represents a novel agent for the treatment of non small cell lung cancer. We demonstrated pronounced anti-proliferative and pro-apoptotic activity in vitro and in vivo as well as the capability to promote physiologic, epithelial differentiation. This implies not only therapeutic, but also preventive potential. Further studies are needed to establish the best possible clinical applications of COH-SR4 in lung cancer.

scholarly journals N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5

2018 ◽  
Vol 45 (5) ◽  
pp. 2054-2070 ◽  
Author(s):  
Ye Liang ◽  
Wenhua Xu ◽  
Shihai Liu ◽  
Jingwei Chi ◽  
Jisheng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Sodium Dodecyl ◽  
Death Receptor ◽  
Small Cell ◽  
Clinical Samples ◽  
Small Cell Lung ◽  
Induced Apoptosis

Background/Aims: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL. Methods: In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo. Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5. After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting. Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope. Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC). O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown. Results: We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis. Furthermore, GlcNAc promoted DR5 clustering by improving its O-glycosylation. Conclusion: These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.

scholarly journals The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer

2009 ◽  
Vol 8 (8) ◽  
pp. 2221-2231 ◽  
Author(s):  
M. Cecilia Crisanti ◽  
Africa F. Wallace ◽  
Veena Kapoor ◽  
Fabian Vandermeers ◽  
Melissa L. Dowling ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Hdac Inhibitor ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung
Sign in / Sign up

Export Citation Format

Share Document