scholarly journals Behavioral Changes in Stem-Cell Potency by HepG2-Exhausted Medium

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1890
Author(s):  
Francesca Balzano ◽  
Giuseppe Garroni ◽  
Sara Cruciani ◽  
Emanuela Bellu ◽  
Silvia Dei Giudici ◽  
...  

Wharton jelly mesenchymal stem cells (WJ-MSCs) are able to differentiate into different cell lineages upon stimulation. This ability is closely related to the perfect balance between the pluripotency-related genes, which control stem-cell proliferation, and genes able to orchestrate the appearance of a specific phenotype. Here we studied the expression of stemness-related genes, epigenetic regulators (DNMT1, SIRT1), miRNAs (miR-145, miR-148, and miR-185) related to stemness, exosomes, the cell-cycle regulators p21 (WAF1/CIP1) and p53, and the senescence-associated genes (p16, p19, and hTERT). Cells were cultured in the presence or absence of the human hepatocarcinoma cell line HepG2-exhausted medium, to evaluate changes in stemness, differentiation capability, and senescence sensibility. Our results showed the overexpression of SIRT1 and reduced levels of p21 mRNA. Moreover, we observed a downregulation of DNMT1, and a simultaneous overexpression of Oct-4 and c-Myc. These findings suggest that WJ-MSCs are more likely to retain a stem phenotype and sometimes to switch to a highly undifferentiable proliferative-like behavior if treated with medium exhausted by human HepG2 cell lines.

2016 ◽  
Vol 213 ◽  
pp. 283-288 ◽  
Author(s):  
Tian-Cheng Li ◽  
Sayaka Yoshizaki ◽  
Tingting Yang ◽  
Michiyo Kataoka ◽  
Tomofumi Nakamura ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2291 ◽  
Author(s):  
Huiliang Song ◽  
Yi Fu ◽  
Dan Wan ◽  
Wenjing Xia ◽  
Fengwei Lyu ◽  
...  

Trichothecene macrolides comprise a class of valuable leading compounds in developing anticancer drugs, however, there are few reports concerning their anticancer mechanisms, especially the anticancer mechanism of the 10,13-cyclotrichothecane derivatives that are found mainly in symbiotic fungi. In vitro anticancer activity of two trichothecene macrolides mytoxin B and myrothecine A against the human hepatocarcinoma cell line SMMC-7721 was investigated in the present study. MTT assay showed that mytoxin B and myrothecine A inhibited the proliferation of SMMC-7721 cells in dose- and time-dependent manners. Annexin V-FITC/PI dual staining assay revealed that mytoxin B and myrothecine A both could induce SMMC-7721 cells apoptosis in a dose-dependent manner. The decreased expression level of anti-apoptotic protein Bcl-2 and the increased expression level of pro-apoptotic protein Bax were observed apparently in Western blot analysis. The reduced ratio of Bcl-2/Bax further confirmed the apoptosis-inducing effect of mytoxin B and myrothecine A on SMMC-7721 cells. Moreover, the expression levels of caspases-3, -8, and -9, and cleaved caspases-3, -8, and -9 were all upregulated in both mytoxin B and myrothecine A-treated cells in Western blot analysis, which indicated that both compounds might induce SMMC-7721 cells apoptosis through not only the death receptor pathway but also the mitochondrial pathway. Finally, mytoxin B and myrothecine A were found to reduce the activity of PI3K/Akt signaling pathway that was similar to the effect of LY294002 (a potent and specific PI3K inhibitor), suggesting that both mytoxin B and myrothecine A might induce SMMC-7721 cells apoptosis via PI3K/Akt pathway.


2020 ◽  
Vol 13 (8) ◽  
pp. 184
Author(s):  
Zikai Feng ◽  
Mohammed Sedeeq ◽  
Abraham Daniel ◽  
Monika Corban ◽  
Krystel L. Woolley ◽  
...  

Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which largely depends on the reversible redox characteristics of the active quinone core. We recently identified 11 naphthoquinone derivatives, 1–11, from a library of SCQs that demonstrated enhanced cytoprotection and improved metabolic stability compared to the clinically used benzoquinone idebenone. Since the toxicity properties of our promising SCQs were unknown, this study developed multiplex methods and generated detailed toxicity profiles from 11 endpoint measurements using the human hepatocarcinoma cell line HepG2. Overall, the toxicity profiles were largely comparable across different assays, with simple standard assays showing increased sensitivity compared to commercial toxicity assays. Within the 11 naphthoquinones tested, the L-phenylalanine derivative 4 consistently demonstrated the lowest toxicity across all assays. The results of this study not only provide useful information about the toxicity features of SCQs but will also enable the progression of the most promising drug candidates towards their clinical use.


2014 ◽  
Author(s):  
Jean Edouard Gairin ◽  
Cedric Lavergne ◽  
Maelle Carraz ◽  
Valérie Jullian ◽  
Geneviève Bourdy ◽  
...  

2008 ◽  
Vol 34 (10) ◽  
pp. 1697-1702 ◽  
Author(s):  
Bao-Jin Zhai ◽  
Ze-Yong Shao ◽  
Chun-Liang Zhao ◽  
Kai Hu ◽  
Ding-Ming Shen ◽  
...  

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