Antiproliferative activity and interactions with cell-cycle related proteins of the organotin compound triethyltin(IV)lupinylsulfide hydrochloride

“…After exposure to each of the stress stimuli under conditions that induce programmed cell death, the number of cells undergoing apoptosis was assayed by staining with propidium iodide and measuring hypodiploid nuclei by flow cytometry (58,66,67). After exposure to hyperosmotic stress (sorbitol treatment), heat shock, UV irradiation, or oxidative stress (H 2 O 2 treatment), populations of cells transfected either with the wild type or with T256D/S422D Sgk displayed a decreased level of apoptosis compared with those transfected with a vector control (Fig.…”

Section: Induction and Localization Of Sgk After Exposure To Environmmentioning

confidence: 99%

Expression of the Serum- and Glucocorticoid-inducible Protein Kinase, Sgk, Is a Cell Survival Response to Multiple Types of Environmental Stress Stimuli in Mammary Epithelial Cells

Leong

Maiyar

Kim

et al. 2003

Journal of Biological Chemistry

221

174

View full text Add to dashboard Cite

The effects of multiple stress stimuli on the cellular utilization of the serum-and glucocorticoid-inducible protein kinase (Sgk) were examined in NMuMg mammary epithelial cells exposed to hyperosmotic stress induced by the organic osmolyte sorbitol, heat shock, ultraviolet irradiation, oxidative stress induced by hydrogen peroxide, or to dexamethasone, a synthetic glucocorticoid that represents a general class of physiological stress hormones. Each of the stress stimuli induced Sgk protein expression with differences in the kinetics and duration of induction and in subcellular localization. The environmental stresses, but not dexamethasone, stimulated Sgk expression through a p38/ MAPK-dependent pathway. In each case, a hyperphosphorylated active Sgk protein was produced under conditions in which Akt, the close homolog of Sgk, remained in its non-phosphorylated state. Ectopic expression of wild type Sgk or of the T256D/S422D mutant Sgk that mimics phosphorylation conferred protection against stress-induced cell death in NMuMg cells. In contrast, expression of the T256A/S422A Sgk phosphorylation site mutant has no effect on cell survival. Sgk is known to phosphorylate and negatively regulate proapoptotic forkhead transcription factor FKHRL1. The environmental stress stimuli that induce Sgk, but not dexamethasone, strongly inhibited the nuclear transcriptional activity and increased the cytoplasmic retention of FKHRL1. Also, the conditional IPTG inducible expression of wild type Sgk, but not of the kinase dead T256A mutant Sgk, protected Con8 mammary epithelial tumor cells from serum starvation-induced apoptosis. Taken together, our study establishes that induction of enzymatically active Sgk functions as a key cell survival component in response to different environmental stress stimuli.

show abstract

“…Organometalic compounds and metal complexes have been gaining growing importance in oncology (Alama et al, 2009), and among organotin compounds, particularly tri-organotin derivatives, have demonstrated cytotoxic properties against a number of tumor cell lines (Barbieri et al, 2001;Barbieri et al, 2002). It is suggested that organotin compounds are involved in cancer treatment via different mechanisms at the molecular level.…”

Section: Antitumor Activity Of Organotin Compounds and Focus In The Fmentioning

confidence: 99%

Triorganotin compounds - ligands for “rexinoid” inducible transcription factors: Biological effects

Brtko

Dvořák

2015

Toxicology Letters

View full text Add to dashboard Cite

Antiproliferative activity and interactions with cell-cycle related proteins of the organotin compound triethyltin(IV)lupinylsulfide hydrochloride

Cited by 31 publications

References 9 publications

Chemical and biotechnological developments in organotin cancer chemotherapy

Chemical and biotechnological developments in organotin cancer chemotherapy

Expression of the Serum- and Glucocorticoid-inducible Protein Kinase, Sgk, Is a Cell Survival Response to Multiple Types of Environmental Stress Stimuli in Mammary Epithelial Cells

Triorganotin compounds - ligands for “rexinoid” inducible transcription factors: Biological effects

Contact Info

Product

Resources

About