Extracellular Signal-Regulated Kinase Is a Target of Cyclooxygenase-1-Peroxisome Proliferator-Activated Receptor-δ Signaling in Epithelial Ovarian Cancer

Daikoku, Takiko; Tranguch, Susanne; Chakrabarty, Anindita; Wang, Dingzhi; Khabele, Dineo; Oršulić, Sandra; Morrow, Jason D.; DuBois, Raymond N.; Dey, Sudhansu K.

doi:10.1158/0008-5472.can-07-0828

Cited by 41 publications

(49 citation statements)

References 46 publications

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“…On the other hand, there is evidence for a role for COX-1, and not COX-2, in some tumors. For example, human and mouse ovarian cancers over-express COX-1, not COX-2 (Daikoku et al, 2006;, and SC560, similar to aspirin (with a preference to inhibit COX-1 over COX-2), reduces the growth of ovarian tumors in mice (Daikoku et al, 2007;Daikoku et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1

Ruud¹,

Nilsson²,

Ruud³

et al. 2013

Brain, Behavior, and Immunity

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, Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1, 2013, Brain, behavior, and immunity, (29) AbstractIt is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexiacachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia-cachexia is unknown. Here, we addressed this issue by transplanting mice with a tumor that elicits anorexia. Meal pattern analysis revealed that the anorexia in the tumor-bearing was due to decreased meal frequency. Treatment with a non-selective COX inhibitor attenuated the anorexia, and also tumor growth. When given at manifest anorexia, non-selective COXinhibitors restored appetite and prevented body weight loss without affecting tumor size.Despite COX-2 induction in the cerebral blood vessels of tumor-bearing mice, a selective COX-2 inhibitor had no effect on the anorexia, whereas selective COX-1 inhibition delayed its onset. Tumor growth was associated with robust increase of PGE 2 levels in plasma -a response blocked both by non-selective COX-inhibition and by selective COX-1 inhibition, but not by COX-2 inhibition. However, there was no increase in PGE 2 -levels in the cerebrospinal fluid. Neutralization of plasma PGE 2 with specific antibodies did not ameliorate the anorexia, and genetic deletion of microsomal PGE synthase-1 (mPGES-1), affected neither anorexia nor tumor growth. Furthermore, tumor-bearing mice lacking EP 4 receptors selectively in the nervous system developed anorexia. These observations suggest that COXenzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE 2 and neuronal EP 4 signaling.

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Section: Discussionmentioning

confidence: 99%

Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1

Ruud¹,

Nilsson²,

Ruud³

et al. 2013

Brain, Behavior, and Immunity

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“…5C). By contrast, treatment with aspirin, an anti-inflammatory drug known to inhibit ovarian tumor cell growth and, in some cases, to activate apoptosis (28,29), did not exert any significant effects (Fig. 5).…”

Section: Acquisition Of Apoptosis Resistance In A2780 Cells Is Associmentioning

confidence: 94%

Trichostatin A up-regulates p73 and induces Bax-dependent apoptosis in cisplatin-resistant ovarian cancer cells

Muscolini

Cianfrocca

Sajeva

et al. 2008

Molecular Cancer Therapeutics

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Several studies in the last years evidenced that deregulation of proapoptotic and antiapoptotic pathways are key players in the onset and maintenance of chemoresistance in advanced ovarian cancers. To characterize the signaling events and molecules involved in the acquisition of cisplatin resistance, we used the human ovarian cancer cell line A2780 and its derivative cisplatin-resistant subline A2780 CIS. We found that the mitochondrial intrinsic apoptotic pathway, induced by cis-dichlorodiammineplatinum (CDDP) in A2780 wild-type cells, was compromised in the resistant subline CIS. The analysis of expression of proteins involved in mitochondriadependent apoptosis revealed a role of Bax and p73 but not p53. Indeed, we found that CDDP treatment induced the up-regulation of p53 in both sensitive and resistant A2780 cell lines. By contrast, p73 and Bax expressions were compromised in resistant cells. Pretreatment of resistant A2780 CIS cells with the histone deacetylase inhibitor trichostatin A overcomes apoptosis resistance to CDDP by restoring both p73 and Bax but not p53 expression. Altogether, these data indicate that p73, but not p53, is involved in the regulation of apoptosis susceptibility to cisplatin in A2780 ovarian cancer cells and evidence a key contribution of histone deacetylase activation in the acquisition of chemotherapy resistance in human ovarian cancer cells.

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“…MEFs were cultured for 24 h in DMEM containing various concentrations of H 2 O 2 , and cell viability was determined with MTT assay as described previously (Promega) (36). To examine the effects of NAC on H 2 O 2 -induced cell damage, MEFs were pretreated with NAC for 24 h and then were treated with H 2 O 2 .…”

Section: Methodsmentioning

confidence: 99%

Uterine FK506-binding protein 52 (FKBP52)–peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress

Hirota

Acar

Tranguch

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Immunophilin FK506-binding protein 52 (FKBP52) is a cochaperone that binds to the progesterone receptor (PR) to optimize progesterone (P 4 )-PR signaling. We recently showed that Fkbp52-deficient (Fkbp52 −/− ) mice have reduced uterine PR responsiveness and implantation failure which is rescued by excess P 4 supplementation in a genetic background-dependent manner. This finding led us to hypothesize that FKBP52 has functions in addition to optimizing PR activity. Using proteomics analysis, we found that uterine levels of peroxiredoxin-6 (PRDX6), a unique antioxidant, are significantly lower in Fkbp52 −/− mice than in WT and PR-null (Pgr −/− ) mice. We also found that Fkbp52 −/− mice with reduced uterine PRDX6 levels are susceptible to paraquat-induced oxidative stress (OS), leading to implantation failure even with P 4 supplementation. The same dose of paraquat did not interfere with implantation in WT mice. Moreover, treatment with antioxidants α-tocopherol and N-acetylcysteine (NAC) attenuated paraquat-induced implantation failure in P 4 -treated Fkbp52 −/− mice. Functional analyses using mouse embryonic fibroblasts show that Fkbp52 deficiency associated with reduced PRDX6 levels promotes H 2 O 2 -induced cell death, which is reversed by the addition of NAC or by forced expression of PRDX6, suggesting that Fkbp52 deficiency diminishes the threshold against OS by reducing PRDX6 levels. These findings provide evidence that heightened uterine OS in Fkbp52 −/− females with reduced PRDX6 levels induces implantation failure even in the presence of excess P 4 . This study shows that FKBP52-PRDX6 signaling protects pregnancy from overt OS.embryo implantation | mouse | uterus

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Extracellular Signal-Regulated Kinase Is a Target of Cyclooxygenase-1-Peroxisome Proliferator-Activated Receptor-δ Signaling in Epithelial Ovarian Cancer

Cited by 41 publications

References 46 publications

Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1

Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1

Trichostatin A up-regulates p73 and induces Bax-dependent apoptosis in cisplatin-resistant ovarian cancer cells

Uterine FK506-binding protein 52 (FKBP52)–peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress

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