G2/M phase

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). 

Figure 5. 2D dotplot, DNA content (x-axis) andBrdU incorporation (y-axis) of HCT-116 cells, treated with SN-38 or edotecarin at lOnM. The cells shown in figure 3 received BrdU pulse at the end of treatment and were processed for BrdU assay. Dot line shown positive cells (S-phase) versus negative cells (Gi and G2/M) phase. 

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. 

Cyciotryprostatins A-C - diketopiperazines that inhibit mammaiian ceii cycie at G2/M phase... 

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... 

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. 

Pyranopyridines 179 and pyranoquinolines 185 are close to chromenes 281 in their mechanism of biological action. Compounds 179 and 185 at micro- and nanomolar concentrations (for the most studied compounds GI50 was about 3-3000 nM) cause arrest of cells in the G2/M phase and inhibit tubuline polymerization (07BML3872, 08JME2561). 

The loss of p5J-dependcnt G, arrest promotes the progression of cells to G2/M phase where they are the target of mitotic arrest. 

Preclinical models have established various methods to increase the cytotoxic activity of radiation therapy. This methodology includes promoting activity against cells in the most radiation-sensitive phase of the cell cycle, the G2/M phase, and eradicating hypoxic tumor cells to decrease radioresistance. The method of radiation therapy (con-... 

Early studies of human lung xenografts demonstrated an increase of cells in the G2/M-phase, after only 1 h of exposure to the lowest dose of SN-38 (the major metabolite of irinotecan) demonstrating promising radiosensitization properties for further study (46). Clinical trials have been initiated (47). 

Fig. 9. The cell cycle. M mitosis G1+S+G2 interphase, i.e., the period between ceU division. During G1 (G for gap) the cellular genome is in the diploid state. This is followed by the S-phase (S for synthesis) during which the DNA is replicated, and finally G2. Insert Cell-cycle analysis of HM02 cells cultured with and without vinblastine. CeU-cycle distribution was determined by staining DNA with propidium iodide, and the number of cells in different phases of the cell cycle was measured with a FACStar flow cytometer. Vinblastine, which disrupts the formation of microtubules, causes cell-cycle arrest in the G2/M-phase...

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