Molecular effects of cyclosporine and oncogenesis: a new model

André, Nayara Delgado; Roquelaure, Bertrand; Conrath, J.

doi:10.1016/j.mehy.2004.03.030

Cited by 44 publications

(26 citation statements)

References 36 publications

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“…However, the immunosuppressive effect and the appearance of de novo cancers hinder the application of CsA in cancer treatment [33], [34]. Recent studies reported that CsA might enhance the chemotherapeutic effect of cytotoxic agents in various cancers [20], [31], [32], [34], whereas HIF-1α knockdown might increase chemo-sensitivity in pancreatic cancer cell line [35].…”

Section: Discussionmentioning

confidence: 99%

CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC

Zhang

Chen

et al. 2014

PLoS ONE

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Hypoxia-inducible factor-1α (HIF-1α) is a highly important transcription factor involved in cell metabolism. HIF-1α promotes glycolysis and inhibits of mitochondrial respiration in pancreatic ductal adenocarcinoma (PDAC). In response to tumor hypoxia, cyclophilin A (CypA) is over-expressed in various cancer types, and is associated with cell apoptosis, tumor invasion, metastasis, and chemoresistance in PDAC. In this study, we showed that both HIF-1α and CypA expression were significantly associated with lymph node metastasis and tumor stage. The expression of CypA was correlated with HIF-1α. Moreover, the mRNA and protein expression of CypA markedly decreased or increased following the suppression or over-expression of HIF-1α in vitro. Chromatin immunoprecipitation analysis showed that HIF-1α could directly bind to the hypoxia response element (HRE) in the CypA promoter regions and regulated CypA expression. Consistent with other studies, HIF-1α and CypA promoted PDAC cell proliferation and invasion, and suppressed apoptosis in vitro. Furthermore, we proved the combination effect of 2-methoxyestradiol and cyclosporin A both in vitro and in vivo. These results suggested that,CypA, a gene downstream of HIF-1α, could promote the development of PDAC. Thus, CypA might serve as a potential therapeutic target for PDAC.

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Section: Discussionmentioning

confidence: 99%

CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC

Zhang

Chen

et al. 2014

PLoS ONE

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“…Its mechanism of action comprises the inhibition of the combination of mitochondrial matrix protein cyclophilin D and the multiprotein complex of the PTP, which effects the closing of the PTP. Interruption of the PTP by CsA is a method for studying the involvement of the PTP in metabolic processes (34). Based on this principle, the present study used CsA to explore the role of the PTP in bufalin-induced apoptosis in U2-OS cells.…”

Section: A B Cmentioning

confidence: 99%

Bufalin induces apoptosis in the U-2OS human osteosarcoma cell line via triggering the mitochondrial pathway

Chen¹,

Li²,

Li³

et al. 2015

Molecular Medicine Reports

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Abstract. Bufalin has been shown to induce apoptosis in osteosarcoma cells; however, the underlying mechanism has not been elucidated. The purpose of the present study was to investigate whether mitochondria-mediated signaling pathways trigger the process of apoptosis in the U-2OS osteosarcoma cell line. Bufalin inhibited the proliferation and induced apoptosis in U-2OS cells in a time-and dose-dependent manner. Bufalin-induced apoptosis was accompanied with a significant reduction of the mitochondrial membrane potential, release of mitochondrial cytochrome c into the cytosol, activation of caspase-3, caspase-9 and poly(adenosine diphosphate ribose) polymerase, as well as downregulation of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein. Cyclosporin A, a specific inhibitor of the mitochondrial permeability transition pore, attenuated bufalin-induced apoptosis. In conclusion, the present study revealed that bufalin induced apoptosis in the U-2OS human osteosarcoma cell line via triggering of the mitochondrial pathway.

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“…First, the ability of immune surveillance for detecting developing tumors and viruses associated with malignant tumors, such as Epstein-Barr virus, may be impaired in immunosuppressive states. Second, immunosuppressive drugs themselves have oncogenic effects, such as a reduction in the ability for DNA repair, induced by cyclosporine [1, 8]. Although such reports are limited in veterinary medicine, a few studies have been reported, in which the incidence of development of malignant tumors, especially lymphoma, was increased by cyclosporine-based immunosuppressive therapy after renal transplantation in cats [16, 24, 25].…”

mentioning

confidence: 99%

Development of hepatocellular carcinoma after long-term immunosuppressive therapy including danazol in a dog

Kobayashi

Miyama

Itamoto

et al. 2016

The Journal of Veterinary Medical Science

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A 2-year-old female beagle was referred to our hospital for evaluation of anemia. Laboratory tests, including bone marrow cytology, revealed non-regenerative immune-mediated anemia (NRIMA). Although initial immunosuppressive multi-drug therapy was not effective, additional administration of danazol was successful in treating the anemia. However, hepatocellular carcinoma (HCC) developed about 20 months after the administration of danazol. In humans, several cases of development of HCC after the administration of danazol have been reported. The present report describes a case of HCC development in a dog after chronic administration of danazol in addition to other immunosuppressive drugs.

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Molecular effects of cyclosporine and oncogenesis: a new model

Cited by 44 publications

References 36 publications

CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC

CypA, a Gene Downstream of HIF-1α, Promotes the Development of PDAC

Bufalin induces apoptosis in the U-2OS human osteosarcoma cell line via triggering the mitochondrial pathway

Development of hepatocellular carcinoma after long-term immunosuppressive therapy including danazol in a dog

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