scholarly journals Activation of Cyclin-dependent Kinase 2 by Full Length and Low Molecular Weight Forms of Cyclin E in Breast Cancer Cells

2003 ◽  
Vol 279 (13) ◽  
pp. 12695-12705 ◽  
Author(s):  
Richard M. Harwell ◽  
Benjamin B. Mull ◽  
Donald C. Porter ◽  
Khandan Keyomarsi
2015 ◽  
Vol 16 (17) ◽  
pp. 7575-7582 ◽  
Author(s):  
Hamed Montazeri ◽  
Saeid Bouzari ◽  
Kayhan Azadmanesh ◽  
Seyed Nasser Ostad ◽  
Mohammad Hossein Ghahremani

Soft Matter ◽  
2020 ◽  
Vol 16 (42) ◽  
pp. 9669-9673
Author(s):  
Dmitry V. Vishnevetskii ◽  
Arif R. Mekhtiev ◽  
Tatyana V. Perevozova ◽  
Dmitry V. Averkin ◽  
Alexandra I. Ivanova ◽  
...  

We present a method for the preparation of a new hydrogel based on low molecular weight gelators that exhibits selective toxicity towards MCF-7 human breast cancer cells.


Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1094 ◽  
Author(s):  
Hsin-Ta Wang ◽  
Po-Chien Chou ◽  
Ping-Han Wu ◽  
Chi-Ming Lee ◽  
Kang-Hsin Fan ◽  
...  

Low-molecular-weight hyaluronic acid (LMWHA) was integrated with superparamagnetic Fe3O4 nanoparticles (Fe3O4 NPs). The size distribution, zeta potential, viscosity, thermogravimetric and paramagnetic properties of the LMWHA-Fe3O4 NPs were systematically examined. For cellular experiments, MCF7 breast cancer cell line was carried out. In addition, the cell targeting ability and characteristics of the LMWHA-Fe3O4 NPs for MCF7 breast cancer cells were analyzed using the thiocyanate method and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The experimental results showed that the LMWHA-Fe3O4 NPs were not only easily injectable due to their low viscosity, but also exhibited a significant superparamagnetic property. Furthermore, the in vitro assay results showed that the NPs had negligible cytotoxicity and exhibited a good cancer cell targeting ability. Overall, the results therefore suggest that the LMWHA-Fe3O4 NPs have considerable potential as an injectable agent for enhanced magnetic resonance imaging (MRI) and/or hyperthermia treatment in breast cancer therapy.


2000 ◽  
Vol 20 (7) ◽  
pp. 2581-2591 ◽  
Author(s):  
Alexander Swarbrick ◽  
Christine S. L. Lee ◽  
Robert L. Sutherland ◽  
Elizabeth A. Musgrove

ABSTRACT The steroid hormone progesterone regulates proliferation and differentiation in the mammary gland and uterus by cell cycle phase-specific actions. The long-term effect of progestins on T-47D breast cancer cells is inhibition of cellular proliferation. This is accompanied by decreased G1 cyclin-dependent kinase (CDK) activities, redistribution of the CDK inhibitor p27Kip1among these CDK complexes, and alterations in the elution profile of cyclin E-Cdk2 upon gel filtration chromatography, such that high-molecular-weight complexes predominate. This study aimed to determine the relative contribution of CDK inhibitors to these events. Following progestin treatment, the majority of cyclin E- and D-CDK complexes were bound to p27Kip1 and few were bound to p21Cip1. In vitro, recombinant His6-p27 could quantitatively reproduce the effects on cyclin E-Cdk2 kinase activity and the shift in molecular weight observed following progestin treatment. In contrast, cyclin D-Cdk4 was not inhibited by His6-p27 in vitro or p27Kip1 in vivo. However, an increase in the expression of the Cdk4/6 inhibitor p18INK4c and its extensive association with Cdk4 and Cdk6 were apparent following progestin treatment. Recombinant p18INK4c led to the reassortment of cyclin-CDK-CDK inhibitor complexes in vitro, with consequent decrease in cyclin E-Cdk2 activity. These results suggest a concerted model of progestin action whereby p27Kip1 and p18INK4c cooperate to inhibit cyclin E-Cdk2 and Cdk4. Since similar models have been developed for growth inhibition by transforming growth factor β and during adipogenesis, interaction between the Cip/Kip and INK4 families of inhibitors may be a common theme in physiological growth arrest and differentiation.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2116
Author(s):  
Xiaoyong Wang ◽  
Lijuan Zhang ◽  
Qi Dai ◽  
Hongzong Si ◽  
Longyun Zhang ◽  
...  

The high concentrations of individual phytochemicals in vitro studies cannot be physiologically achieved in humans. Our solution for this concentration gap between in vitro and human studies is to combine two or more phytochemicals. We screened 12 phytochemicals by pairwise combining two compounds at a low level to select combinations exerting the synergistic inhibitory effect of breast cancer cell proliferation. A novel combination of luteolin at 30 μM (LUT30) and indole-3-carbinol 40 μM (I3C40) identified that this combination (L30I40) synergistically constrains ERα+ breast cancer cell (MCF7 and T47D) proliferation only, but not triple-negative breast cancer cells. At the same time, the individual LUT30 and I3C40 do not have this anti-proliferative effect in ERα+ breast cancer cells. Moreover, this combination L30I40 does not have toxicity on endothelial cells compared to the current commercial drugs. Similarly, the combination of LUT and I3C (LUT10 mg + I3C10 mg/kg/day) (IP injection) synergistically suppresses tumor growth in MCF7 cells-derived xenograft mice, but the individual LUT (10 mg/kg/day) and I3C (20 mg/kg/day) do not show an inhibitory effect. This combination synergistically downregulates two major therapeutic targets ERα and cyclin dependent kinase (CDK) 4/6/retinoblastoma (Rb) pathway, both in cultured cells and xenograft tumors. These results provide a solid foundation that a combination of LUT and I3C may be a practical approach to treat ERα+ breast cancer cells after clinical trials.


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