G2/M phase cell cycle

Dolastatin 15 (213) Depsipeptide Tasidotin (Synthadotin, ILX-651) (214) Oncology Induces G2/M phase cell cycle arrest by inhibiting tubulin assembly Phase II Genzyme 952-954... 

Powolny and Singh (2008) have studied extensively on the mechanism of cell cycle arrest with DATS using human prostate cancer cells (PC-3 and DU 145). The DATS-mediated G2/M phase cell cycle arrest in prostate cancer cells was associated with reactive oxygen species (ROS)-dependent hyperphosphorylation and destruction of the cell division cycle 25C (Cdc25C) phosphatase (Xiao et al. 2005). Interestingly, the cell cycle arrest with DATS appeared to be selective for cancer cells, since a normal prostate epithelial cell line was resistant to cell cycle arrest with DATS (Xiao etal. 2005). They also demonstrated that the ROS generation by DATS treatment in prostate cancer cells is caused by an increase... 

Xiao, D., Herman-Antosiewicz, A., Antosiewicz, J., Xiao, H., Brisson, M., Lazo, J.S., and Singh, S.V. 2005. Diallyl trisulfide-induced G2-M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of... 

Two groups demonstrated that BRCA-1- and BRCA-2-deficient cells are acutely sensitive to PARPi [11,12]. Potent inhibitors like KU0058684 (5), KU0058948 (6), and AG14361 (26) were cytotoxic at nanomolar concentrations in HR-defective cells, and displayed excellent selectivity for BRCA-1- and BRCA-2-deficient cells over wild-type cells. After 24 h of exposure, 5 elicited G2 or M phase cell cycle arrest and a tetraploid DNA content. The applicability of this discovery was revealed when BRCA-2-deficient and BRCA-2-proficient cells were injected into mice and tumors were allowed to develop. Daily treatment with 5 or 26 had no effect on the BRCA-2 wild-type cells however, when BRCA-2-deficient cells were treated with PARPi, no tumors developed. 

Figure 5.3 DNA flow cytometric analysis of cells treated with apigenin for 24 or 48 h. Each point represents the mean SD of three independent experiments. Cell cycle was monitored by a DNA flow cytometric analysis indicating as follows 0,% of G1-phase cells A,% of S-phase cells % of G2/M-phase cells. Means SD from three independent experiments are shown. p < 0.05 and p < 0.01 vs. the vehicle controls. (From Wang et at, Molecular Carcinogenesis, 28, 102-110, 2000. With permission.)...

Figure 1 Overview of the different phases of the cell cycle. Quiescent cells are in GO phase and reenter the cell cycle at Gl during which cells prepare for DNA synthesis. After passing the restriction point in late Gl cells are committed to enter S phase, during which DNA replication occurs. Cells in G2 phase prepare for mitosis (M phase). Cell cycle progression is controlled by various positive and negative cell cycle regulatory proteins including cyclins (A, B, D, E) cyclin dependent kinases (cdk 1,2, 4, 6) cdk inhibitors (p15, p16, p18, p19, p21, p27, p57), retinoblastoma (Rb) and p53.

Cell cycle cytotoxity - in vitro (G1 and G2 + M Phases, cell culture) at 100.0 pg/mL, CA-Ovarian-O-342 and CA-Ovarian-O-342/Cisplatin resistant (G2 Phase, cell culture) in vitro at 2.0 pM, Leuk-P388 and Leuk-P388 (ADR-resistant). Compound enhanced effect of adriamydn or effect seen only when compound and adriamydn exposure were concurrent. Cytotoxic - in vitro (Cell culture, Leuk-L1210), cone, used not stated sarcoma-9 and cells-monkey-kidney-CV-1 (at 50.0 pg/mL). 

The phenanthroindolizidine alkaloid (-)-antofine (95) exhibits high cytotoxicity to drug-sensitive and multidrug-resistant cancer cells by arresting the G2/M phase of the cell cycle. In the first asymmetric total synthesis of (-)-95, the late-stage construction of pyrrolidine 94 for the final Pictet-Spengler cyclo-methylenation to 95 was performed by RCM and subsequent hydrogenation (Scheme 18) [67]. 

HASEGAWA T, NisHiNO H and IWASHIMA A (1993) Isothiocyauates inhibit cell cycle progression of HeLa cells at G2/M phase . Anticancer Drugs, 4 273-9. 

In a recent study, the antiproliferative effect of different carotenoids, including (3-carotene, lycopene and lutein, on PCNA and cyclin Dl expression in human KB cells have been studied. The results indicate that carotenoids suppressed cell growth by acting as inhibitors of the expressions of PCNA and cyclin Dl, although in a different extent (Cheng et al., 2007). On the other hand, (3-carotene was able to induce a cell cycle delay in G2/M phase by decreasing the expression of cyclin A in human colon adenocarcinoma cells (Palozza et al., 2002a). 

Several mechanisms have been shown to regulate the activity of the SCF complex. The expression of F-box proteins such as Skp2 is regulated by cell-cycle-dependent transcription [4]. The expression of Skp2 is high in late Gl, S, and G2/M phase but... 

Mahalingam, S., Ayyavoo, V., Patel, M., Kieber-Emmons, T., Kao, G. D., Muschel, R. j., Weiner, D. B. HlV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle. Proc. Natl. Acad. Sci. USA 1998, 95, 3419-3424. 

Several bis(dioxopiperazines) exhibit antitumor activity. Thus, ICRF 159 122 is an inhibitor of DNA synthesis, blocks the cell cycle in G2-M phase and inhibits metastases in the Lewis lung tumor (3LL) animal model without impeding the... 

MCF-7 cells exposed to 50 nM TSA were in G1 phase (>70%). However, cells treated with 1 J,M TSA arrested cells predominantly in G2/M phase, suggesting a dose-dependent fashion. With either dose, cells accumulated least in the S phase. In addition to accumulation of hyperacetylated nucleosome core histones, TSA enhanced p21 expression. Therefore, flow cytometry (FACS) offers an efficient tool for analyzing the action of HDACIs in cell proliferation. This method is particularly useful for application to clinical samples, where cell numbers may be small. The effects of HDACIs on the cell cycle are dose-dependent. 

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