Malignant growth of arsenic-transformed cells depends on activated Akt induced by reactive oxygen species

Author(s):  
Qun Lou ◽  
Fuxun Chen ◽  
Bingyang Li ◽  
Meichen Zhang ◽  
Fanshuo Yin ◽  
...  
2008 ◽  
Vol 21 (12) ◽  
pp. 1561-1570 ◽  
Author(s):  
Victor P. Bulgakov ◽  
Dmitry L. Aminin ◽  
Yuri N. Shkryl ◽  
Tatiana Y. Gorpenchenko ◽  
Galina N. Veremeichik ◽  
...  

It is known that expression of the Agrobacterium rhizogenes rolC gene in transformed plant cells causes defense-like reactions, such as increased phytoalexin production and expression of pathogenesis-related proteins. In the present study, we examined whether this phenomenon is associated with increased production of reactive oxygen species (ROS). Single-cell assays based on confocal microscopy and fluorogenic dyes (2,7-dichlorofluorescein diacetate and dihydrorhodamine 123) showed reduced steady-state levels of ROS in rolC-expressing Rubia cordifolia cells as compared with normal cells. Paraquat, a ROS inducer, caused significant ROS elevation in normal cells but had little effect on rolC-transformed cells. Likewise, ROS elevation triggered by a light stress was suppressed in transformed cells. Our results indicate that the rolC gene acts as a ROS suppressor in unstressed cells and its expression prevents stress-induced ROS elevations. We detected a two- to threefold increase in tolerance of rolC-transformed cells to salt, heat, and cold treatments. Simultaneously, rolC-transformed cells maintained permanently active defensive status, as found by measuring isochorismate synthase gene expression and anthraquinone production. Thus, the oncogene provoked multiple effects in which ROS production and phytoalexin production were clearly dissociated.


2003 ◽  
Vol 37 (6) ◽  
pp. 611-619 ◽  
Author(s):  
Antonio Macho ◽  
Rocío Sancho ◽  
Alberto Minassi ◽  
Giovanni Appendino ◽  
Alfons Lawen ◽  
...  

2008 ◽  
Vol 94 (2) ◽  
pp. 278-283 ◽  
Author(s):  
Peter Scharff ◽  
Uwe Ritter ◽  
Olga P Matyshevska ◽  
Svitlana V Prylutska ◽  
Iryna I Grynyuk ◽  
...  

An increase of the intracellular reactive oxygen species (ROS) concentration leads to the development of oxidative stress and, thus, to the damage of cell components. The cause-and-effect relations between these processes have not been fully established yet. The ability of photo excited supramolecular composites containing fullerenes C60 immobilized at nanosilica particles to generate reactive oxygen species (ROS) in cells of two types (rat thymocytes, and transformed cells of ascite Erlich carcinoma, EAC, and leucosis L1210) is demonstrated. The damaging effect of photo excited C60-composites are shown, which appeared to be selective and manifested in transformed cells, but not in thymocytes. It has been shown that after the irradiation of aqueous solutions or cell suspensions in the presence of fullerene C60, the generation of reactive oxygen species is observed. It has been shown that the influence of photo excited fullerene C60 on metabolic processes depends on the composition of C60-containing complex and on the type of the cells. The damaging effects of photo excited fullerene C60-containing composites were demonstrated to be selective. The data presented suggest that the application of fullerene C60-containing composites for the selective activation of ROS-dependent death program in certain types of tumor cells is very promising.


2008 ◽  
Vol 44 (4) ◽  
pp. 624-634 ◽  
Author(s):  
Jung-A Choi ◽  
Eun-Young Kim ◽  
Haiwon Song ◽  
Cheolmin Kim ◽  
Jae-Hong Kim

1999 ◽  
Vol 6 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Antonio Macho ◽  
Marco A Calzado ◽  
Juan Muñoz-Blanco ◽  
Consuelo Gómez-Díaz ◽  
Consuelo Gajate ◽  
...  

2015 ◽  
Vol 35 (21) ◽  
pp. 3646-3656 ◽  
Author(s):  
Daniel J. Garama ◽  
Tiffany J. Harris ◽  
Christine L. White ◽  
Fernando J. Rossello ◽  
Maher Abdul-Hay ◽  
...  

Increased production of mitochondrion-derived reactive oxygen species (ROS) is characteristic of a metabolic shift observed during malignant transformation. While the exact sources and roles of ROS in tumorigenesis remain to be defined, it has become clear that maintaining redox balance is critical for cancer cell proliferation and survival and, as such, may represent a vulnerability that can be exploited therapeutically. STAT3, a latent cytosolic transcription factor activated by diverse cytokines and growth factors, has been shown to exhibit an additional, nontranscriptional function in mitochondria, including modulation of electron transport chain activity. In particular, malignant transformation by Ras oncogenes exploits mitochondrial STAT3 functions. We used mass spectrometry-based metabolomics profiling to explore the biochemical basis for the STAT3 dependence of Ras transformation. We identified the gamma-glutamyl cycle, the production of glutathione, and the regulation of ROS as a mitochondrion-STAT3-dependent pathway in Ras-transformed cells. Experimental inhibition of key enzymes in the glutathione cycle resulted in the depletion of glutathione, accumulation of ROS, oxidative DNA damage, and cell death in an oncogenic Ras- and mitochondrial STAT3-dependent manner. These data uncover a synthetic lethal interaction involving glutathione production and mitochondrial ROS regulation in Ras-transformed cells that is governed by mitochondrial STAT3 and might be exploited therapeutically.


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