Dexamethasone Decreases Hepatocellular Carcinoma Cell Sensitivity to Cisplatin-Induced Apoptosis

Yang, Nanying; Zhang, Haibin; Sima, Hui; Fu, Yong; Zhao, Wenchao; Li, Dongyu; Yang, Guanhu

doi:10.5754/hge11153

Cited by 12 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GCs have been demonstrated to protect normal tissue which may be good for patients, but the protection of cancer cells may impair the effect of chemotherapy [27]. Thus, it is understandable that the appeal for reevaluating the administration of GCs in the management of solid cancer patients has emerged recently.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Reduces Sensitivity to Cisplatin by Blunting p53-Dependent Cellular Senescence in Non-Small Cell Lung Cancer

Wang

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

IntroductionDexamethasone (DEX) co-treatment has proved beneficial in NSCLC patients, improving clinical symptoms by the reduction of side effects after chemotherapy. However, recent studies have shown that DEX could render cancer cells more insensitive to cytotoxic drug therapy, but it is not known whether DEX co-treatment could influence therapy-induced senescence (TIS), and unknown whether it is in a p53-dependent or p53-independent manner.MethodsWe examined in different human NSCLC cell lines and detected cellular senescence after cisplatin (DDP) treatment in the presence or absence of DEX. The in vivo effect of the combination of DEX and DDP was assessed by tumor growth experiments using human lung cancer cell lines growing as xenograft tumors in nude mice.ResultsCo-treatment with DEX during chemotherapy in NSCLC resulted in increased tumor cell viability and inhibition of TIS compared with DDP treated group. DEX co-treatment cells exhibited the decrease of DNA damage signaling pathway proteins, the lower expression of p53 and p21CIP1, the lower cellular secretory program and down-regulation of NF-κB and its signaling cascade. DEX also significantly reduced DDP sensitivity in vivo.ConclusionsOur results underscore that DEX reduces chemotherapy sensitivity by blunting therapy induced cellular senescence after chemotherapy in NSCLC, which may, at least in part, in a p53-dependent manner. These data therefore raise concerns about the widespread combined use of gluocorticoids (GCs) with antineoplastic drugs in the clinical management of cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Dexamethasone Reduces Sensitivity to Cisplatin by Blunting p53-Dependent Cellular Senescence in Non-Small Cell Lung Cancer

Wang

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…17,18 Glucocorticoid-dependent death or survival is directly associated with the selective expression of the short or long isoforms of Bcl-X (Bcl-X S or Bcl-X L ), which are pro-and antiapoptotic, respectively. 17 Cells resistant to glucocorticoid-induced apoptosis, such as some cancer cells 19,20 and fibroblasts, 21 show increased production of Bcl-X L . In the hippocampus, where they induce cell death, glucocorticoids increase the ratio of the proapoptotic molecule Bax relative to the antiapoptotic molecule Bcl-X L .…”

Section: Discussionmentioning

confidence: 99%

Mifepristone, a Blocker of Glucocorticoid Receptors, Promotes Photoreceptor Death

Cubilla¹,

Bermúdez²,

Marquioni-Ramella³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. Glucocorticoids are best known by their protective effect on retinal photoreceptor damage. However, they could also be involved in photoreceptor homeostasis under basal, nonstressful conditions. Therefore, we aimed to study glucocorticoid-induced changes of survival-related molecules in male mice retinas under standard illumination conditions (12 hours light, 60 lux/12 h dark).METHODS. Male Balb-c mice were injected with dexamethasone (DEX), a selective glucocorticoid receptor a (GRa) agonist, its antagonist mifepristone (MFP), or both drugs (DþM) at noon. A group of mice was subjected to surgical adrenalectomy (AdrX). Retinas were studied by histology, immunohistochemistry, TUNEL procedure, and Western blotting at different periods after pharmacological or surgical intervention (6 hours, 48 hours, or 7 days). RESULTS.The antiapoptotic molecule Bcl-X L significantly increased 6 hours after DEX injection. By contrast, this molecule could no longer be found after MFP injection. At the same time, high levels of cleaved caspase-3 (CC-3) and Bax appeared in retinal extracts, and TUNEL þ nuclei selectively showed in the outer nuclear layer (ONL). After MFP, retinal extracts also contained phosphorylated histone H2AX (p-H2AX), a marker of DNA breakage and repair. Loss of ONL nuclear rows and decrease of rhodopsin levels were evident 7 days after MFP administration. These changes were minimized when DEX was given together with MFP (DþM). In the absence of MFP, DEX increased Bcl-X L in every retinal layer, with a marked intensification in photoreceptor inner segments. Numerous TUNEL þ nuclei rapidly appeared in the ONL after AdrX. CONCLUSIONS.A single dose of MFP induced selective photoreceptor damage in the absence of other environmental stressors. Because damage was prevented by DEX, and was reproduced by AdrX, our findings suggest that glucocorticoids play a critical role in photoreceptor survival. (Invest Ophthalmol Vis Sci. 2013;54:313-322)

show abstract

“…However, dexamethasone was found to inhibit apoptosis in TGF-beta treated rat hepatoma cells, also likely by increasing Bcl-xL expression in these cells [115]. Several other studies have shown glucocorticoids to be protective in hepatoma carcinoma cells against other apoptotic stimuli [116,117]. Glucocorticoid treatment may also be particularly detrimental in breast cancer.…”

Section: Anti-apoptotic Effects Of Glucocorticoid Signalingmentioning

confidence: 99%

Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword

Gruver-Yates

Cidlowski

2013

Cells

129

View full text Add to dashboard Cite

First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis and outline what is known about the apoptotic response in cells and tissues of the body after exposure to glucocorticoids. Glucocorticoid-induced apoptosis affects the skeletal system, muscular system, circulatory system, nervous system, endocrine system, reproductive system, and the immune system. Interestingly, several cell types have an anti-apoptotic response to glucocorticoids that is cytoprotective. Lastly, we will discuss the pro- and anti-apoptotic effects of glucocorticoids in cancers and their clinical implications.

show abstract

Dexamethasone Decreases Hepatocellular Carcinoma Cell Sensitivity to Cisplatin-Induced Apoptosis

Abstract: DEX can decrease hepatocellular carcinoma cell sensitivity to CIS-induced cell death by preventing cell apoptosis.

Cited by 12 publications

References 0 publications

Dexamethasone Reduces Sensitivity to Cisplatin by Blunting p53-Dependent Cellular Senescence in Non-Small Cell Lung Cancer

Dexamethasone Reduces Sensitivity to Cisplatin by Blunting p53-Dependent Cellular Senescence in Non-Small Cell Lung Cancer

Mifepristone, a Blocker of Glucocorticoid Receptors, Promotes Photoreceptor Death

Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword

Contact Info

Product

Resources

About