Caspase-1α Is Down-regulated in Human Ovarian Cancer Cells and the Overexpression of Caspase-1α Induces Apoptosis

Feng, Qi Sheng; Pei-xiang, LI; Salamanca, Clara; Huntsman, David; Leung, Peter C.K.; Auersperg, Nelly

doi:10.1158/0008-5472.can-05-0239

Cited by 37 publications

(32 citation statements)

References 18 publications

(20 reference statements)

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“…Although CASP1 is well known as one of the cytokine-processing caspases for producing IL-1ß and IL-18, it also plays a major role in apoptosis and is linked to certain pathologic conditions (29,30). The downregulation of CASP1 is particularly associated with the occurrence of human ovarian cancer, with overexpression of CASP1 triggering apoptosis (24). However, our results revealed overexpression of CASP1 in cancerous ovaries of chickens compared with normal ovaries and detected CASP1 mRNA in cancerous ovaries.…”

Section: Discussioncontrasting

confidence: 55%

“…In light of induction of apoptosis by CASP1, CASP1 may also contribute to the removal of damaged cells generated by continuous ovulation. Likewise, CASP1 is highly expressed in CaOV3 human ovarian cancer cells, and CASP1-dependent apoptosis is dysregulated (24). It is hypothesized that the dysregulation of the intrinsic apoptosis pathway, which includes BID cleavage stimulated by CASP1, is subsequently able to survive damaged cells and could increase the risk of cancer incidence.…”

Section: Discussionmentioning

confidence: 99%

“…CASP2, CASP8, CASP9 and CASP10 are initiator caspases, and CASP3, CASP6 and CASP7 are effector caspases (23). Known as interleukin 1ß converting enzyme, CASP1 plays an important role in both apoptosis and inflammation (24). Apoptosis is regulated by stepwise activation of caspases for the processing or cleaving of other caspases (25).…”

Section: Introductionmentioning

confidence: 99%

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The expression profile of apoptosis-related genes in the chicken as a human epithelial ovarian cancer model

et al. 2010

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Abstract. The purpose of our study was to examine the expression pattern of apoptosis-related genes in normal and cancerous ovaries of the hen. Localization of apoptosis-related gene mRNA was investigated in cancerous ovaries using in situ hybridization. The expression patterns of apoptosis-related genes were confirmed with RT-PCR in normal and cancerous ovaries. Differences of expression level between normal ovaries and ovarian cancers were analyzed using quantitative RT-PCR. In both normal and cancerous chicken ovaries, the expression of CASP1, CASP2, CASP3, CASP6, CASP8 and CASP9 were detected through RT-PCR analysis. The expression of BCL2, BCL2L1 and BID were confirmed in normal and cancerous ovaries of the hen. Quantitative RT-PCR showed that CASP1 expression was significantly increased in cancerous ovaries compared with normal ovaries, whereas BID expression was decreased. Our results showed a resistance to removal of abnormal cells via apoptosis in cancerous ovaries of the hen. Collectively, this phenomenon is closely associated with the dysregulation of CASP1 and BID expression in chicken ovarian cancer.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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The expression profile of apoptosis-related genes in the chicken as a human epithelial ovarian cancer model

et al. 2010

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“…Another enzyme, topoisomerase II, was subject to investigation, with the genes topoisomerase II alpha and topoisomerase II beta being upregulated in ovarian cancer; topoisomerase II beta was considered to have potential as a novel chemotherapeutic target (Withoff et al 1999). Furthermore, the enzyme caspase 1-α has been discovered as pro-apoptotic in ovarian cancer cells and its down-regulation in these cells was suggested as a factor in the resistance of ovarian cancer cells to apoptosis (Feng et al 2005).…”

Section: Biomarkers and Signallingmentioning

confidence: 99%

Bioinformatic Analysis for the Validation of Novel Biomarkers for Cancer Diagnosis and Drug Sensitivity

Lockwood¹

2015

Fields: Journal of Huddersfield Student Research

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Background: The genetic control of tumour progression presents the opportunity for bioinformatics and gene expression data to be used as a basis for tumour grading. The development of a genetic signature based on microarray data allows for the development of personalised chemotherapeutic regimes. Method: ONCOMINE was utilised to create a genetic signature for ovarian serous adenocarcinoma and to compare the expression of genes between normal ovarian and cancerous cells. Ingenuity Pathways Analysis was also utilised to develop molecular pathways and observe interactions with exogenous molecules. Results:The gene signature demonstrated 98.6% predictive capability for the differentiation between borderline ovarian serous neoplasm and ovarian serous adenocarcinoma. The data demonstrated that many genes were related to angiogenesis. Thymidylate synthase, GLUT-3 and HSP90AA1 were related to tanespimycin sensitivity (p=0.005). Conclusions: Genetic profiling with the gene signature demonstrated potential for clinical use. The use of tanespimycin alongside overexpression of thymidylate synthase, GLUT-3 and HSP90AA1 is a novel consideration for ovarian cancer treatment.

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“…It was recently demonstrated that caspase-1 is an upstream positive regulator of caspase-6-mediated cell death in primary human neurons (Guo et al, 2006). Further, caspase-1 promotes apoptosis in cancer cells (Feng et al, 2005). In addition, the expression of caspases is spatially and temporally regulated, depending on the cell type and development stage.…”

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confidence: 99%

Game and Players: Mitochondrial Apoptosis and the Therapeutic Potential of Ursodeoxycholic Acid

Solá

Aranha

Steer³

et al. 2007

Current Issues in Molecular Biology

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Apoptosis represents a universal and exquisitely efficient cellular suicide pathway essential for a variety of normal biological processes ranging from embryonic development to ageing. In fact, tissue homeostasis is dependent on the perfect balance between positive and negative signals that determines the decision between life and death. Therefore, any imbalance can result in a wide range of pathologic disorders associated with unwanted apoptosis or cell growth. During the apoptotic process, the molecular players interact closely with each other in ways relevant to accelerate or interrupt the cellular death process. In addition, two major pathways of apoptosis activation have been recognized as the "intrinsic" mitochondrial pathway and the "extrinsic" death receptor pathway. Although these pathways act independently to initiate apoptosis, a delicate balance and cross-talk between the extrinsic and intrinsic pathways is thought to occur in many cell types. Interestingly, we have shown that ursodeoxycholic acid (UDCA), an endogenous hydrophilic bile acid, is a potent inhibitor of apoptosis by either stabilizing the mitochondrial membrane or modulating the expression of specific upstream targets. Herein, we review the main effectors involved in the death machinery, describe how they interact to regulate apoptosis, and discuss the main pathways that control cell death and survival. Further, we address multiple interesting targets as well as the potential application of UDCA as a therapeutic modality for apoptosis-related disorders. IntroductionThe process of cell death typically follows one of two patterns: necrosis or apoptosis (Bayerdorffer et al., 1993). The first is the consequence of acute metabolic perturbation as it occurs in ischemia/reperfusion or acute drug-induced toxicity. In contrast, apoptosis represents the execution of a death program often initiated by specific stimuli. Nevertheless, it is important to note that, in certain occasions, rather than separate entities, apoptosis and necrosis are frequently the consequence of the same initiating factors and signaling pathways, representing extremes on a continuum of cell death (Bull et al., 1983;Hofmann, 2002).Apoptosis is an active mechanism by which metazoan organisms quickly eliminate cells in response 124 Solá et al.The molecular mechanisms of programmed cell death are highly conserved throughout evolution. Studies in Caenorhabditis elegans (C. elegans) have demonstrated that cell demise is carried out by specific cellular pathways (Hall et al., 1997), suggesting that it may be more "programmed" than initially thought. In fact, cell death in C. elegans is regulated only by three genes: ced-3, ced-4 and ced-9 (Fig. 1). Further, Egl-1 blocks the activity of Ced-9, an inhibitor of Ced-4 that complexes with and activates the cysteinic protease Ced-3 (Conradt and Horvitz, 1998).The apoptosis process can be subdivided into initiation, effector and degradation phases (Kroemer et al., 1995). In mammalian cells, the initiation stage depends on the ty...

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Caspase-1α Is Down-regulated in Human Ovarian Cancer Cells and the Overexpression of Caspase-1α Induces Apoptosis

Cited by 37 publications

References 18 publications

The expression profile of apoptosis-related genes in the chicken as a human epithelial ovarian cancer model

The expression profile of apoptosis-related genes in the chicken as a human epithelial ovarian cancer model

Bioinformatic Analysis for the Validation of Novel Biomarkers for Cancer Diagnosis and Drug Sensitivity

Game and Players: Mitochondrial Apoptosis and the Therapeutic Potential of Ursodeoxycholic Acid

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