Search results for "Cell cycle checkpoint"
showing 10 items of 126 documents
Ionizing radiation but not anticancer drugs causes cell cycle arrest and failure to activate the mitochondrial death pathway in MCF-7 breast carcinom…
2001
There is considerable evidence that ionizing radiation (IR) and chemotherapeutic drugs mediate apoptosis through the intrinsic death pathway via the release of mitochondrial cytochrome c and activation of caspases -9 and -3. Here we show that MCF-7 cells that lack caspase-3 undergo a caspase-dependent apoptotic cell death in the absence of DNA fragmentation and alpha-fodrin cleavage following treatment with etoposide or doxorubicin, but not after exposure to IR. Re-expression of caspase-3 restored DNA fragmentation and alpha-fodrin cleavage following drug treatment, but it did not alter the radiation-resistant phenotype of these cells. In contrast to the anticancer drugs, IR failed to induc…
Abstract 4662: Shikonin causes cancer cell death by inducing mitochondrial dysfunction
2012
Abstract Shikonin, a naturally occurring napthoquinone, has been used in herbal formulations for the treatment of several inflammatory diseases in Traditional Chinese Medicine since decades. In recent studies, shikonin revealed remarkable anticancer activities and thereby is a promising candidate for cancer chemotherapy. However, the underlying cellular mechanisms and targets of shikonin are still unknown. Here, we showed that shikonin indeed exhibits strong cytotoxic effects on a panel of 15 different cancer cell lines also containing multi-drug resistant cells. The strongest effects were obtained on U937 leukemia cells. To better understand the underlying mechanisms, we performed a whole …
Bortezomib: a new pro-apoptotic agent in cancer treatment.
2010
Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IkappaB breakdown and the related stabilization of NFkappaB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved…
Abstract 6327: Artesunate reduces tumor growth and induces different kinds of cell death in docetaxel-resistant prostate carcinoma cells
2020
Abstract Introduction: Prostate carcinoma (PCa) is the most common cancer in men. The therapeutic effect of approved compounds, such as docetaxel, is limited due to the development of therapy resistance, making new treatment options essential. Artesunate (ART), used in Traditional Chinese Medicine, has shown anti-tumor activity in several tumor types. However, little is known about the efficacy of ART on therapy-resistant PCa. Therefore, the impact of ART on docetaxel-resistant PCa cells was investigated. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, and LNCaP, were exposed to ART [1-100 µM] for 24, 48, or 72 hours. Cells not exposed to ART …
Abstract 1423: Shikonin impairs the growth of docetaxel-resistant prostate cancer cells by necroptosis
2021
Abstract Introduction: Prostate carcinoma (PCa) is the most common malignancy in men. Androgen-targeted therapy and chemotherapy are currently the treatment of choice for advanced stages. Due to resistance towards these therapies, prognosis remains poor and new treatment options are urgently required. Shikonin (SHI) from Traditional Chinese Medicine (TCM) might be promising, since it induces anti-tumor effects in different tumor entities. However, data on PCa are few, and data on resistant PCa are not existent. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1 - 1.5 μM] for 24, 48, or 72 hours. Untreated…
Cyclin dependent kinase-1 (Cdk-1) inhibition as a novel therapeutic strategy against pancreatic ductal adenocarcinoma (pdac)
2021
Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in humans, due to late diagnosis and limited treatment possibilities. Improved treatment for PDAC patients is warranted. Cyclin-dependent kinase 1 (CDK1) is a stimulator of cell cycle progression and its activity is regularly enhanced in pancreatic cancer cells. Therefore, CDK1 has been proposed as a novel drug target to treat patients with PDAC. This review describes the potential of CDK1 inhibition as a treatment for PDAC by outlining the molecular pathways influenced by CDK1 inhibition and new therapeutic strategies. Abstract The role of CDK1 in PDAC onset and development is two-fold. Firstly, since …
Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D
2017
A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress
2012
Abstract Background The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints) mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK) cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism. Results This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses.…
Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsenti…
2014
A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G 2 /M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr 34 and to increase the cytotoxic activity of paclit…
Cytolethal distending toxin (CDT): a bacterial weapon to control host cell proliferation ?
2001
Cytolethal distending toxins (CDT) constitute a family of genetically related bacterial protein toxins able to stop the proliferation of numerous cell lines. This effect is due to their ability to trigger in target cells a signaling pathway that normally prevents the transition between the G2 and the M phase of the cell cycle. Produced by several unrelated Gram-negative mucosa-associated bacterial species, CDTs are determined by a cluster of three adjacent genes (cdtA, cdtB, cdtC) encoding proteins whose respective role is not yet fully elucidated. The CDT-B protein presents sequence homology to several mammalian and bacterial phosphodiesterases, such as DNase I. The putative nuclease activ…