ERβ up-regulation was involved in silibinin-induced growth inhibition of human breast cancer MCF-7 cells

2016 ◽  
Vol 591 ◽  
pp. 141-149 ◽  
Author(s):  
Nan Zheng ◽  
Lu Liu ◽  
Weiwei Liu ◽  
Ping Zhang ◽  
Huai Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Human Breast Cancer ◽  
Human Breast ◽  
Mcf 7

Growth inhibition, G1-arrest, and apoptosis in MCF-7 human breast cancer cells by novel highly lipophilic 5-fluorouracil derivatives

2004 ◽  
Vol 22 (4) ◽  
pp. 379-389 ◽  
Author(s):  
Juan Antonio Marchal ◽  
Houria Boulaiz ◽  
Inés Suárez ◽  
Estrella Saniger ◽  
Joaquín Campos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
G1 Arrest ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

Nanoparticle-Aptamer: An Effective Growth Inhibitor for Human Cancer Cells

2009 ◽  
Author(s):  
Kok Hao Chen ◽  
Jong Hyun Choi
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cell Viability ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Semiconductor Nanocrystals ◽  
Human Breast ◽  
Dna Concentration ◽  
Mcf 7

Semiconductor nanocrystals have unique optical properties due to quantum confinement effects, and a variety of promising approaches have been devised to interface the nanomaterials with biomolecules for bioimaging and therapeutic applications. Such bio-interface can be facilitated via a DNA template for nanoparticles as oligonucleotides can mediate the aqueous-phase nucleation and capping of semiconductor nanocrystals.[1,2] Here, we report a novel scheme of synthesizing fluorescent nanocrystal quantum dots (NQDs) using DNA aptamers and the use of this biotic/abiotic nanoparticle system for growth inhibition of MCF-7 human breast cancer cells for the first time. Particularly, we used two DNA sequences for this purpose, which have been developed as anti-cancer agents: 5-GGT GGT GGT GGT TGT GGT GGT GGT GG-3 (also called, AGRO) and 5-(GT)15-3.[3–5] This study may ultimately form the basis of unique nanoparticle-based therapeutics with the additional ability to optically report molecular recognition. Figure 1a shows the photoluminescence (PL) spectra of GT- and AGRO-passivated PbS QD that fluoresce in the near IR, centered at approximately 980 nm. A typical synthesis procedure involves rapid addition of sodium sulfide in the mixture solution of DNA and Pb acetate at a molar ratio of 2:4:1. The resulting nanocrystals are washed to remove unreacted DNA and ions by adding mixture solution of NaCl and isopropanol, followed by centrifugation. The precipitated nanocrystals are collected and re-suspended in aqueous solution by mild sonication. Optical absorption measurements reveal that approximately 90 and 77% of GT and AGRO DNA is removed after the washing process. The particle size distribution in Figure 1b suggests that the GT sequence-capped PbS particles are primarily in 3–5 nm diameter range. These nanocrystals can be easily incorporated with mammalian cells and remain highly fluorescent in sub-cellular environments. Figure 1c serially presents an optical image of a MCF-7 cell and a PL image of the AGRO-capped QD incorporated with the cell. Figure 1. (a) Normalized fluorescence spectra of PbS QD synthesized with GT and AGRO sequences, which were previously developed as anti-cancer agents. The DNA-capped QD fluoresce in the near IR centered at ∼980 nm. (b) TEM image of GT-templated nanocrystals ranging 3–5 nm in diameter. (c) Optical image of an MCF-7 human breast cancer cell after a 12-hour exposure to aptamer-capped QD. (d) PL image of AGRO-QD incorporated with the cell, indicating that these nanocrystals remain highly fluorescent in sub-cellular environments. One immediate concern for interfacing inorganic nanocrystals with cells and tissue for labeling or therapeutics is their cytotoxicity. The nanoparticle cytotoxicity is primarily determined by material composition and surface chemistry, and QD are potentially toxic by generating reactive oxygen species or by leaching heavy metal ions when decomposed.[6] We examined the toxicity of aptamer-passivated nanocrystals with NIH-3T3 mouse fibroblast cells. The cells were exposed to PbS nanocrystals for 2 days before a standard MTT assay as shown in Figure 2, where there is no apparent cytotoxicity at these doses. In contrast, Pb acetate exerts statistically significant toxicity. This observation suggests a stable surface passivation by the DNA aptamers and the absence of appreciable Pb2+ leaching. Figure 2. Viability of 3T3 mouse fibroblast cells after a 2-day exposure to DNA aptamer-capped nanocrystals. There is no apparent dose-dependent toxicity, whereas a statistically significant reduction in cell viability is observed with Pb ions. Note that Pb acetate at 133 μM is equivalent to the Pb2+ amount that was used for PbS nanocrystal synthesis at maximum concentration. Error bars are standard deviations of independent experiments. *Statistically different from control (p<0.005). Finally, we examined if these cyto-compatible nanoparticle-aptamers remained therapeutically active for cancer cell growth inhibition. The MTT assay results in Figure 3a show significantly decreased growth of breast cancer cells incorporated with AGRO, GT, and the corresponding templated nanocrystals, as anticipated. In contrast, 5-(GC)15-3 and the QDs synthesized with the same sequence, which were used as negative controls along with zero-dose control cells, did not alter cell viability significantly. Here, we define the growth inhibition efficacy as (100 − cell viability) per DNA of a sample, because the DNA concentration is significantly decreased during the particle washing. The nanoparticle-aptamers demonstrate 3–4 times greater therapeutic activities compared to the corresponding aptamer drugs (Figure 3b). We speculate that when a nanoparticle-aptamer is internalized by the cancer cells, it forms an intracellular complex with nucleolin and nuclear factor-κB (NF-κB) essential modulator, thereby inhibiting NF-κB activation that would cause transcription of proliferation and anti-apoptotic genes.[7] The nanoparticle-aptamers may more effectively block the pathways for creating anti-apoptotic genes or facilitate the cellular delivery of aptamers via nanoparticle uptake. Our additional investigation indicates that the same DNA capping chemistry can be utilized to produce aptamer-mediated Fe3O4 nanocrystals, which may be potentially useful in MRI and therapeutics, considering their magnetic properties and biocompatibility. In summary, the nanoparticle-based therapeutic schemes developed here should be valuable in developing a multifunctional drug delivery and imaging agent for biological systems. Figure 3. Anti-proliferation of MCF-7 human breast cancer cells with aptamer-passivated nanocrystals. (a) Viability of MCF-7 cells exposed to AGRO and GT sequences, and AGRO-/GT-capped QD for 7 days. The DNA concentration was 10 uM, while the particles were incubated with cells at 75 nM. (b) Growth inhibition efficacy is defined as (100 − cell viability) per DNA to correct the DNA concentration after particle washing.

2,3,6- Tribromo- 4,5- dihydroxybenzyl Methyl Ether Induces Growth inhibition and apoptosis in MCF-7 human breast cancer cells

2007 ◽  
Vol 30 (9) ◽  
pp. 1132-1137 ◽  
Author(s):  
Ji-Hyeon Lee ◽  
Sang Eun Park ◽  
Mohammad Akbar Hossain ◽  
Min Young Kim ◽  
Mi-Na Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Methyl Ether ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
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Crosstalk with insulin and dependence on PI3K/Akt/mTOR rather than MAPK pathways in upregulation of basal growth following long-term oestrogen deprivation in three human breast cancer cell lines

2011 ◽  
Vol 5 (2) ◽  
Author(s):  
Swagat Ray ◽  
Philippa D. Darbre
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Human Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Oestrogen Deprivation ◽  
Mcf 7

Abstract: MCF-7, T-47-D, ZR-75-1 human breast cancer cell lines are dependent on oestrogen for growth but can adapt to grow during long-term oestrogen deprivation. This serves as a model for identification of therapeutic targets in endocrine-resistant breast cancer.: An overlooked complication of this model is that it involves more than non-addition of oestrogen, and inadequate attention has been given to separating molecular events associated with each of the culture manipulations.: Insulin and oestradiol were shown to protect MCF-7 cells against upregulation of basal growth, demonstrating a crosstalk in the growth adaptation process. Increased phosphorylation of p44/42MAPK and c-Raf reflected removal of insulin from the medium and proliferation of all three cell lines was inhibited to a lesser extent by PD98059 and U0126 following long-term oestrogen/insulin withdrawal, demonstrating a reduced dependence on the MAPK pathway. By contrast, long-term oestrogen/insulin deprivation did not alter levels of phosphorylated Akt and did not alter the dose-response of growth inhibition with LY294002 in any of the three cell lines. The IGF1R inhibitor picropodophyllin inhibited growth of all MCF-7 cells but only in the long-term oestrogen/insulin-deprived cells was this paralleled by reduction in phosphorylated p70S6K, a downstream target of mTOR. Long-term oestrogen/insulin-deprived MCF-7 cells had higher levels of phosphorylated p70S6K and developed increased sensitivity to growth inhibition by rapamycin.: The greater sensitivity to growth inhibition by rapamycin in all three cell lines following long-term oestrogen/insulin deprivation suggests rapamycin-based therapies might be more effective in breast cancers with acquired oestrogen resistance.

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