Search results for "wt"
showing 10 items of 5424 documents
COX-2-dependent and COX-2-independent mode of action of celecoxib in human liver cancer cells.
2011
Celecoxib (Celebrex((R)), Pfizer) is a selective cyclooxygenase-2 (COX-2) inhibitor with chemopreventive and antitumor effects. However, it is now well known that celecoxib has several COX-2-independent activities. To better understand COX-2-independent molecular mechanisms underlying the antitumor activity of celecoxib, we investigated the expression profile of the celecoxib-treated COX-2-positive (Huh7) and COX-2-negative (HepG2) liver cancer cell lines, using microarray analysis. Celecoxib treatment resulted in significantly altered expression levels of 240 and 403 transcripts in Huh7 and HepG2 cells, respectively. Confirmation of the microarray results was performed for selected genes b…
Biological activities of the LXRα and β agonist, 4β-hydroxycholesterol, and of its isomer, 4α-hydroxycholesterol, on oligodendrocytes: effects on cel…
2013
The biochemical and biological properties of 4β-hydroxycholesterol and of its isomer, 4α-hydroxycholesterol, are not well known. So, we determined the ability of 4α- and 4β-hydroxycholesterol to react with LXRα and LXRβ, and we characterized the activities of these oxysterols on oligodendrocytes which are myelin synthesizing cells. The effects of 4α- and 4β-hydroxycholesterol were studied on 158N murine oligodendrocytes to assess their activities on cell growth and viability, oxidative and inflammatory status. To this end different parameters were used: cell counting with trypan blue; identification of dead cells and cell cycle analysis with propidium iodide; evaluation of mitochondrial dep…
Insulin and IGFs induce apoptosis in chick embryo retinas deprived of L-glutamine
1999
In chick embryo retinas, cultured in serum-free medium lacking L-glutamine, IGF-I, IGF-II and insulin induced apoptotic DNA fragmentation and cell death, IGF-I being the most efficacious compound. The apoptotic effect, which was particularly evident in retinas removed from 7-day-old chick embryos, declined with the age of the embryos and disappeared after day 11. Apoptosis appeared after a time lag of 8 h and then increased with time up to 16 h. Cycloheximide, an inhibitor of protein synthesis, was capable of entirely abolishing apoptotic cell death. The effect induced by IGFs or insulin was suppressed by the addition of glutamine. Cytokine-mediated apoptosis was also observed after withdra…
Control of Programmed Cell Death by Distinct Electrical Activity Patterns
2010
Electrical activity and sufficient supply with survival factors play a major role in the control of apoptosis in the developing cortex. Coherent high-frequency neuronal activity, which efficiently releases neurotrophins, is essential for the survival of immature neurons. We studied the influence of neuronal activity on apoptosis in the developing cortex. Dissociated cultures of the newborn mouse cerebral cortex were grown on multielectrode arrays to determine the activity patterns that promote neuronal survival. Cultures were transfected with a plasmid coding for a caspase-3-sensitive fluorescent protein allowing real-time analysis of caspase-3-dependent apoptosis in individual neurons. Ele…
Primary proliferating immature myeloid cells from CML patients are not resistant to induction of apoptosis by DNA damage and growth factor withdrawal.
1996
Induction of apoptosis by growth factor deprivation or gamma-irradiation-induced DNA damage was directly studied in proliferating primary haemopoietic cells derived from CD34-positive cells of 13 CML patients and 12 normal controls. CD34-positive cells were cultured in the presence of appropriate concentrations of SCF and G-CSF for 5–7 d. After gamma irradiation with 500 rad or growth factor deprivation, the fraction of apoptotic cells was assessed by two independent methods applying either measurement of cells incorporating FITC-labelled dUTP by terminal transferase or assessment of the fraction of cells with a less than 2N DNA content in flow cytometry. Proliferating CML cells were not re…
A petrol ether extract of the roots of Onosma paniculatum induces cell death in a caspase dependent manner
2010
Traditional Chinese medicine (TCM) has become very popular in Western countries during the last years. Zicao, a remedy of TCM, has been traditionally used to treat cancer, and, its main constituents, naphthoquinones, have been reported to possess antitumor activity (Chen et al., 2002; Papageorgiou et al., 1999). Here, we prepared extracts of different polarities of Onosma paniculatum Bur.Franch., a plant which is amongst others used as Zicao, but, much less investigated. The extracts were analyzed concerning their growth inhibitory and apoptosis-inducing activity in various tumor cells.Cell viability was measured by XTT viability and a growth inhibition assay. Effects on the cell cycle and …
Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes
2008
Apoptosis, or programmed cell death, regulates tissue development and homeostasis in multi-cellular organisms. Extrinsic or intrinsic death signals activate pro-apoptotic pathways, resulting in the activation of caspases and finally in cell death. An important event during apoptosis process is the permeabilization of the outer mitochondrial membrane (OMM). Integrity of the OMM is regulated by the Bcl-2 protein family, which is divided into three groups: anti-apoptotic members Bcl-2, Bcl-xL and myeloid cell leukemia-1 (Mcl-1), pro-apoptotic multidomain members Bax and Bak, and pro-apoptotic BH3-only proteins. Mitochondrial activation is regulated by selective interactions of Bcl-2 proteins v…
Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O6-methylguanine triggered apoptosis, DSBs and chromosomal aberrations by …
2008
Abstract O 6 -methylguanine (O 6 MeG) is a highly critical DNA adduct induced by methylating carcinogens and anticancer drugs such as temozolomide, streptozotocine, procarbazine and dacarbazine. Induction of cell death by O 6 MeG lesions requires mismatch repair (MMR) and cell proliferation and is thought to be dependent on the formation of DNA double-strand breaks (DSBs) or, according to an alternative hypothesis, direct signaling by the MMR complex. Given a role for DSBs in this process, either homologous recombination (HR) or non-homologous end joining (NHEJ) or both might protect against O 6 MeG. Here, we compared the response of cells mutated in HR and NHEJ proteins to temozolomide and…
Synthesis of Triazenoazaindoles: a New Class of Triazenes with Antitumor Activity
2011
Despite improvements in the treatment and prevention of cancer, the number of new diagnoses continues to rise; this has fuelled substantial interest in the development of new and effective chemotherapeutic agents. Compounds of the triazene class, such as dacarbazine, have been used in the clinical management of many cancer types including brain, leukemia, and melanoma. A new compound class bearing a triazenoazaindole scaffold was synthesized with the aim of identifying new antiproliferative agents. Compounds 5 a-g and 6 a-c were screened against a panel of human tumor cell lines, and two of them, 5 e and 5 f, showed cytotoxicity (GI(50) range: 2.2-8.2 μM) in all cell lines. These two compou…
Role of caspase-8 in hepatocyte response to infection and injury in mice.
2007
Caspase-8 has been implicated in signaling for apoptotic cell death and for certain nonapoptotic functions. However, knowledge of actual physiological or pathophysiological processes to which this enzyme contributes is lacking. Using a mouse model and employing the conditional knockout approach to delete the caspase-8 gene specifically in the liver, we found that caspase-8 deficiency in hepatocytes facilitates infection of the liver by Listeria monocytogenes, attenuates the hepatocyte proliferation wave during the first 48 hours after partial hepatectomy and, depending on the genetic background of the mice, prompts a chronic inflammatory response to the hepatectomy, as a result of which the…