Search results for "Cell cycle checkpoint"
showing 10 items of 126 documents
All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions …
2012
Objective: All-trans retinoic acid (ATRA) has been demonstrated to inhibit tumor growth by restoration of gap junctional intercellular communication (GJIC) via upregulation of connexin (Cx) expression in some solid tumors. However, the relationship between ATRA and GJIC remains unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the effect of ATRA on the GJIC function of OSCC. Study design: We measured the effects of ATRA on the viability and cell cycle distribution of SCC9 and Tca8113 OSCC cells. The GJIC function was observed using the scrape-loading dye transfer technique, and the mRNA and protein levels of Cx32 and Cx43 were detected by qRT-PCR, West…
Lanostanoids from fungi: a group of potential anticancer compounds.
2012
Lanostanes are a group of tetracyclic triterpenoids derived from lanosterol. They have relevant biological and pharmacological properties, such as their cytotoxic effects via induction of apoptosis. This review compiles the most relevant lanostanoids studied from 2000 to 2011, principally those isolated from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata, which have great potential as anticancer agents because of their cytotoxic or apoptotic effects. The compounds were selected on the basis of their proapoptotic mechanisms, through their ability to modify transcription…
Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?
2015
Recent clinical trials revealed the impressive efficacy of immunological checkpoint blockade in different types of metastatic cancers. Such data underscore that immunotherapy is one of the most promising strategies for cancer treatment. In addition, preclinical studies provide evidence that some cytotoxic drugs have the ability to stimulate the immune system, resulting in anti-tumor immune responses that contribute to clinical efficacy of these agents. These observations raise the hypothesis that the next step for cancer treatment is the combination of cytotoxic agents and immunotherapies. The present review aims to summarize the immune-mediated effects of chemotherapeutic agents and their …
Pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles, a New Class of Antimitotic Agents Active against Multiple Malignant Cell Types
2020
A new class of pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles was synthesized for the treatment of hyperproliferative pathologies, including neoplasms. The new compounds were screened in the 60 human cancer cell lines of the NCI drug screen and showed potent activity with GI50 values reaching the nanomolar level, with mean graph midpoints of 0.08-0.41 μM. All compounds were further tested on six lymphoma cell lines, and eight showed potent growth inhibitory effects with IC50 values lower than 500 nM. Mechanism of action studies showed the ability of the new [1,2]oxazoles to arrest cells in the G2/M phase in a concentration dependent manner and to induce apoptosis through the mitochondrial…
Lack of Association Between Tumor Oxygenation and Cell Cycle Distribution or Proliferation Kinetics in Experimental Sarcomas
2003
In tumor cells, pronounced hypoxia induces an arrest of cell cycle in the late G1phase1−3. Since hypoxia is a common phenomenon in experimental and human tumors the hypoxia-induced disturbance of the cell cycle may play a role in the reduced efficacy of non-surgical treatment modalities resulting in a reduced long-term prognosis and a higher rate of local recurrences in hypoxic tumors4,5. It has been shown that a cell cycle arrest reduces the efficacy of standard radiotherapy6,7 and may alter the cytotoxic effects of various chemotherapeutic agents such as cisplatin, alkylating agents, doxorubicin or taxols8−12 and of cytokines13. If tumor hypoxia plays a relevant role in affecting the cell…
Cytotoxicity and modes of action of five Cameroonian medicinal plants against multi-factorial drug resistance of tumor cells
2013
Abstract Ethnopharmacological relevance Beilschmiedia acuta Kosterm, Clausena anisata (Willd) Hook, Fagara tessmannii Engl., Newbouldia laevis Seem., and Polyscias fulva (Hiern) Harms. are medicinal plants used in Cameroonian traditional medicine in the treatment of various types of cancers. The present study aims at investigating 11 methanolic extracts from the above Cameroonian medicinal plants on a panel of human cancer cell lines, including various drug-resistant phenotypes. Possible modes of action were analyzed for two extracts from Beilschmiedia acuta and Polyscia fulva and alpha-hederin, the representative constituent of Polyscia fulva. Materials and methods Cytotoxicity was determi…
MAP kinase p38 and its relation to T cell anergy and suppressor function of regulatory T cells
2008
Diverse regulatory T cell populations (Treg) are important for the control of self tolerance and immune homeostasis. These include naturally occurring CD4+CD25+ Treg (nTreg) and induced Treg (iTreg). Tolerogenic dendritic cells, modulated by IL-10, are able to convert peripheral T cells into iTreg. These are anergic and characterized by a G(1) cell cycle arrest, dependent on elevated levels of the cdk inhibitor p27(Kip1). Novel data revealed a distinct pattern of MAP kinase activation in iTreg different from clonal T cell anergy, with enhanced activation of the p38-MAPKAP-K2/3 pathway. p38 is involved in cell cycle control and its activity is a prerequisite for the induction and maintenance…
Miltirone Induces G2/M Cell Cycle Arrest and Apoptosis in CCRF-CEM Acute Lymphoblastic Leukemia Cells
2015
Miltirone (1) is a diterpene quinone extracted from a well-known Chinese traditional herb (Salvia miltiorrhiza). We investigated the cytotoxic effects of miltirone toward sensitive and multidrug-resistant acute lymphoblastic leukemia cell lines. Miltirone inhibited multidrug-resistant P-glycoprotein (P-gp)-overexpressing CEM/ADR5000 cells better than drug-sensitive CCRF-CEM wild-type cells, a phenomenon termed collateral sensitivity. Flow cytometric analyses revealed that miltirone induced G2/M arrest and apoptosis. Furthermore, miltirone stimulated reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) disruption, which in turn induced DNA damage and activation…
Specific Irreversible Cell-Cycle Arrest and Depletion of Cancer Cells Obtained by Combining Curcumin and the Flavonoids Quercetin and Fisetin.
2022
Background: Induced senescence could be exploited to selectively counteract the proliferation of cancer cells and target them for senolysis. We examined the cellular senescence induced by curcumin and whether it could be targeted by fisetin and quercetin, flavonoids with senolytic activity. Methods: Cell-cycle profiles, chromosome number and structure, and heterochromatin markers were evaluated via flow cytometry, metaphase spreads, and immunofluorescence, respectively. The activation of p21waf1/cip1 was assessed via RT-qPCR and immunoblotting. Senescent cells were detected via SA-β-Galactosidase staining. Results: We report that curcumin treatment specifically triggers senescence in cancer…
Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence
2020
AbstractTranscriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a]P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a]P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-me…