Search results for "cell cycle."

Inhibition of colon cancer growth by docosahexaenoic acid involves autocrine production of TNFα

2016

IF 7.932; International audience; The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-cancer properties. Among pro-inflammatory mediators, tumor necrosis factor a (TNF alpha) plays a paradoxical role in cancer biology with induction of cancer cell death or survival depending on the cellular context. The objective of the study was to evaluate the role of TNFa in DHA-mediated tumor growth inhibition and colon cancer cell death. The treatment of human colorectal cancer cells, HCT-116 and HCT-8 cells, with DHA triggered apoptosis in autocrine TNF alpha-dependent manner. We demonstrated that DHA-induced increased content of TNF alpha mRNA occurred thr…

Roles of TP53 in determining therapeutic sensitivity, growth, cellular senescence, invasion and metastasis.

2016

TP53 is a critical tumor suppressor gene that regulates cell cycle progression, apoptosis, cellular senescence and many other properties critical for control of normal cellular growth and death. Due to the pleiotropic effects that TP53 has on gene expression and cellular physiology, mutations at this tumor suppressor gene result in diverse physiological effects. T53 mutations are frequently detected in numerous cancers. The expression of TP53 can be induced by various agents used to treat cancer patients such as chemotherapeutic drugs and ionizing radiation. Radiation will induce Ataxia telangiectasia mutated (ATM) and other kinases that results in the phosphorylation and activation of TP53…

The hallmarks of ovarian cancer: proliferation and cell growth

2020

Epithelial ovarian cancer (EOC) is a heterogeneous group of diseases with distinct biological and clinical behaviour. Despite the differences between them, the capability of tumour cells to continuously proliferate and avoid death is maintained among histotypes. This ability is the result of alterations at different levels, causing the deregulation of cell cycle and proliferative-related pathways. Even if the leading role is played by RB and TP53, changes in other molecular pathways are involved in the development of EOC. This ability can be exploited to generate in vitro and in vivo models resembling the conditions of tumour development in a patient. In vivo models, such as patient-derived…

Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload

2017

Induction of the cell cycle is emerging as an intervention to treat heart failure. Here, we tested the hypothesis that enhanced cardiomyocyte renewal in transgenic mice expressing cyclin D2 would be beneficial during hemodynamic overload. We induced pressure overload by transthoracic aortic constriction (TAC) or volume overload by aortocaval shunt in cyclin D2-expressing and WT mice. Although cyclin D2 expression dramatically improved survival following TAC, it did not confer a survival advantage to mice following aortocaval shunt. Cardiac function decreased following TAC in WT mice, but was preserved in cyclin D2-expressing mice. On the other hand, cardiac structure and function were compr…

2020

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Rather, resistance develops under chronic drug use, prompting many patients to lower their relapse risk by turning to natural, plant-derived products. The present study was designed to evaluate whether the natural compound, sulforaphane (SFN), combined with the mTOR inhibitor everolimus, could block the growth and proliferation of bladder cancer cells in the short- and long-term. The bladder cancer cell lines RT112, UMUC3, and TCCSUP were exposed short- (24 h) or long-term (8 weeks) to ev…

Beauvericin and enniatin B effects on a human lymphoblastoid Jurkat T-cell model

2018

Abstract Several mycotoxins exert their effect on the immunological system; some are classified as immunotoxic. Jurkat T-cells were used to study toxic effects of beauvericin (BEA) and enniatin B (ENN B). Both are not legislated mycotoxins with increasing presence in feed and food. Concentrations studied were from 1 to 15 μM at 24, 48 and 72 h. Cell death by increasing the percentage of apoptotic/necrotic cells was: BEA > ENN B. IC50 values ranged from 3 to 7.5 μM for BEA. ENN B 15 μM decreased viability (21-29%). The percentage of apoptotic/necrotic cells was BEA > ENN B at 24 h but not at 48 h. Caspase-3&7 activation profile varied, although both mycotoxins increased this activation. No d…

Chemopreventive Property of Sencha Tea Extracts towards Sensitive and Multidrug-Resistant Leukemia and Multiple Myeloma Cells

2020

The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically,…

Antiproliferative effect of plant sterols at colonic concentrations on Caco-2 cells

2017

Abstract Plant sterols (PS) have been incorporated to foods due to their cholesterol-lowering effect. Because of their low intestinal absorption (0.5–2%), they can reach the colon and exert local actions. The aim of this study was to evaluate the antiproliferative effect of individual (β-sitosterol, campesterol and stigmasterol) and combined PS in colon cancer cells (Caco-2) at human colonic concentrations after simulated gastrointestinal digestion of a PS enriched milk-based fruit beverage. β-Sitosterol, campesterol and stigmasterol induced significant cell viability reduction (13–59% vs control), but only stigmasterol produced an overproduction of reactive oxygen species (92% vs control).…

Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound

2016

Abstract A natural like O -glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N -(3-methyl-1-(4-nitrophenyl)-1 H -pyrazol-5-yl)acetamide. The glycosyl derivative 4 showed antiproliferative activity against all the tumoral cell lines of the NCI panel in the range 0.47–5.43  μ M. Cytofluorimetric analysis performed on MDA-MB231, a very aggressive breast cancer cell line, which does not express estrogen, progesterone and HER-2/neu receptors, showed that 4 is able to induce prolonged cell cycle arrest at G2/M phase and morphological signs of differentiation. These events are correlated with down-regulation of both cyclin B1 and cdc2, the cyclins involved in…

CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin

2021

Summary Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless…