scholarly journals Cycling cytoplasmic factors that promote mitosis in the cultured 2-cell mouse embryo

Development ◽  
1988 ◽  
Vol 104 (1) ◽  
pp. 115-120
Author(s):  
H.P. Pratt ◽  
A.L. Muggleton-Harris

A cytoplasmic component(s), previously shown to rescue the ‘blocked’ 2-cell mouse embryo in vitro, has been demonstrated to peak in activity during the transition between G2 and M phase and decline thereafter. The possible significance of this component(s) in the regulation of cleavage of the cultured mouse embryo is discussed.

Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 191-207
Author(s):  
W. J. D. Reeve

Cells of the 16-cell mouse embryo endocytose horseradish peroxidase (HRP) which becomes localized in most cases to a juxtanuclear position. Cells that have ingested HRP in intact embryos, and cells dissociated from embryos prior to culture in HRP, showed similar patterns of cytoplasmic distribution of the ingested enzyme. Cells in the embryo in situ were incubated in HRP, and then labelled with fluorescent antibody either before (to label the outside surface of the embryo) or after (to reveal populations of outer polar and inner apolar cells) their disaggregation into single cells. The population of polar outside cells from the morula includes more cells with a highly restricted localization of HRPcontaining vesicles than does the population of inside cells, and this restricted localization underlies the exposed surface or pole of the cell. A 2/16 couplet formed by division in vitro of a 1/8 cell is comparable to the pairs of cells dissociated from 16-cell embryos; most couplets from either source consisted of a larger cell that showed polarized surface binding of fluorescent ligand (fluorescent pole) and a smaller cell with a uniform distribution of bound ligand. The incidence of restricted patterns of HRP staining was highest among populations of both larger and polar cells. When 1/8 cells labelled with HRP are observed during division to 2/16, the previously clustered vesicles of ingested HRP become more dispersed throughout the cytoplasm and, although the two cells of some couplets can stain differently very soon after their formation, the patterns of distribution of HRP take about 1 h after division to stabilize. These observations are consistent with cells of the 16-cell embryo inheriting different features of cytoplasmic organization.


Author(s):  
Mingliang Fan ◽  
Jiping Li

Background: The combination of two or more therapeutic drugs is an attractive approach to improve the treatment of experimental tumors. Leveraging nanocarriers for combinational drug delivery can allow a control over drug biological fate and promote co-localization in the same area of the body. However, there are certain concerns regarding the biodegradability and potential long-term toxicity arising from these synthetic nanoscale carriers. Objective: Our aim was to develop a combinational nanodrug delivery system formed by self-assembling of amphiphilic drug molecules,minimizing potential toxicities associated with using additional synthetic nanocarriers. Methods: A novel prodrug chlorambucil gemcitabine conjugate was synthesized, this prodrug was used for the encapsulation of an additional hydrophobic anticancer drug paclitaxel, taking the form of combinational nanodrugs. Particle size and zeta potential were evaluated, cytotoxicity assay and apoptosis/cell cycle analysis were also performed to validate the anticancer efficacy of the combinational nanodrugs. Results: The combinational nanodrugs were acquired by means of nanoprecipitation. In A549 lung adenocarcinoma cell line, cellular assays revealed that co-delivery of low dosage paclitaxel with chlorambucil gemcitabine conjugate can act synergistically to inhibit cell growth and induce accumulation of cells in the G2/M phase with a concomitant decrease in G0/G1 compartment. Conclusion: Chlorambucil gemcitabine conjugate and paclitaxel can co-assemble into composite nanoparticles by a nanoprecipitation process and the resulting combinational nanodrugs showed synergistic anticancer effect. This synthetic nanocarrier-free approach might broaden the nanodrug concept and have potential in cancer therapy.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Fuli Li ◽  
Tinglei Huang ◽  
Yao Tang ◽  
Qingli Li ◽  
Jianzheng Wang ◽  
...  

AbstractUtidelone (UTD1), a novel microtubule stabilizing agent, is an epothilone B analogue which was produced by genetic engineering. UTD1 has exhibited broad antitumor activity in multiple solid tumors. However, its activity and mechanism in colorectal cancer (CRC) remain to be studied. In this study, UTD1 dramatically inhibited CRC cell proliferation (with 0.38 µg/ml, 0.77 µg/ml IC50 in RKO and HCT116, respectively) in vitro. Immunofluorescence staining showed that UTD1 induced the formation of microtubule bundling and asters in RKO cells. Flow cytometry analysis demonstrated that UTD1 induced cell cycle to arrest in G2/M phase, subsequent apoptosis. Significantly, UTD1 exhibited stronger effect on inducing apoptosis than paclitaxel and 5-FU, especially in HCT15 cells which is ABCB1 high-expression. UTD1 exposure cleaved caspase-3 and poly ADP-ribose polymerase (PARP), decreased mitochondrial membrane potential, released cytochrome c, increased the production of active oxygen and activated c-Jun N-terminal kinase (JNK), suggesting ROS/JNK pathway was involved in this process. Moreover, UTD1 inhibited tumor growth and was more effective and safer compared with paclitaxel and 5-FU in RKO xenograft in nude mice. Taken together, our findings first indicate that UDT1 inhibits tumor growth in CRC xenograft model and may be a promising agent for CRC treatment.


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