Tissue inhibitor of metalloproteinase-1 decreased chemosensitivity of MDA-435 breast cancer cells to chemotherapeutic drugs through the PI3K/AKT/NF-кB pathway

2011 ◽  
Vol 65 (3) ◽  
pp. 163-167 ◽  
Author(s):  
Z.Y. Fu ◽  
J.H. Lv ◽  
C.Y. Ma ◽  
D.P. Yang ◽  
T. Wang
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Chemotherapeutic Drugs ◽  
Tissue Inhibitor

scholarly journals GSK-3β Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutraceuticals

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 816
Author(s):  
Stephen L. Abrams ◽  
Shaw M. Akula ◽  
Akshaya K. Meher ◽  
Linda S. Steelman ◽  
Agnieszka Gizak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Cancer Cells ◽  
Mitochondrial Respiration ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Drugs ◽  
Pancreatic Cancers ◽  
Signal Transduction Inhibitors ◽  
Gsk 3Β ◽  
Mcf 7

Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3β in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3β. Transfection of MIA-PaCa-2 cells with WT-GSK-3β increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3β often increased therapeutic sensitivity. An exception was observed with cells transfected with WT-GSK-3β and sensitivity to the BCL2/BCLXL ABT737 inhibitor. WT-GSK-3β reduced glycolytic capacity of the cells but did not affect the basal glycolysis and mitochondrial respiration. KD-GSK-3β decreased both basal glycolysis and glycolytic capacity and reduced mitochondrial respiration in MIA-PaCa-2 cells. As a comparison, the effects of GSK-3 on MCF-7 breast cancer cells, which have mutant PIK3CA, were examined. KD-GSK-3β increased the resistance of MCF-7 cells to chemotherapeutic drugs and certain signal transduction inhibitors. Thus, altering the levels of GSK-3β can have dramatic effects on sensitivity to drugs and signal transduction inhibitors which may be influenced by the background of the tumor.

Development of Self-Assembled Biomimetic Boc-Protected Peptide-Polymer Based Nanovehicles for Targeted Delivery to Tumor Cells

2016 ◽  
Vol 29 ◽  
pp. 33-53 ◽  
Author(s):  
Alexandra M. Brown ◽  
Yoliem S. Miranda-Alarćon ◽  
Grant A. Knoll ◽  
Steven M. Romanelli ◽  
Ipsita A. Banerjee
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Breast Cancer Cells ◽  
Dermal Fibroblasts ◽  
Burst Release ◽  
Chemotherapeutic Drugs ◽  
New Family

Although effective, chemotherapeutic drugs often cause undesired side-effects. Thus, encapsulating chemotherapeutic drugs into nanoscale drug delivery vehicles (DDVs) has the potential to reduce side effects and promote targeted delivery. By mimicking ABA like block-co-polymer systems, we have developed a new amphiphilic biomimetic co-polymer Boc-Ile-PEG-Ile-Boc which was found to readily self-assemble into nanomicelles within hydrophilic shell structures. To facilitate targeting tumor cells, the nanoassemblies were bound to folate, leading to the formation of core shell like structures (IBP-F). Gold nanoparticles (AuNPs), were then embedded followed by functionalization with a second layer of folate. The final DDV system abbreviated (IBP-F-Au-F) formed a multi-layered nanostructure that was capable of efficiently encapsulating the anti-tumor drug tamoxifen. For comparison, we also examined the efficacy of the IBP-F assemblies as DDVs in the absence of AuNPs and a second folate layer. Release profiles showed an initial burst release, followed by sustained release. The DDVs were found to be biocompatible. Upon encapsulating the DDVs with tamoxifen, cell proliferation was inhibited over a period of 72 hours for both DDVs, while non-cancerous dermal fibroblasts continued to proliferate, thus indicating specific targeting ability of the DDVs. Confocal microscopy studies conducted in the presence of human breast cancer cells, MDA-MDB 231 revealed that the drug loaded assemblies were successfully internalized within the cells. SPR analysis demonstrate that IBP-F-Au-F had a higher affinity for breast cancer cells over non-cancerous keratinocyte cells. Thus, we have developed a new family of DDVs that selectively targets tumor cells.

VIP receptor antagonists and chemotherapeutic drugs inhibit the growth of breast cancer cells

2001 ◽  
Vol 68 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Terry W. Moody ◽  
Julius Leyton ◽  
Daniel Chan ◽  
Douglas C. Brenneman ◽  
Mati Fridkin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Drugs ◽  
Receptor Antagonists ◽  
Vip Receptor

scholarly journals Artichoke Polyphenols Sensitize Human Breast Cancer Cells to Chemotherapeutic Drugs via a ROS-Mediated Downregulation of Flap Endonuclease 1

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Maria Mileo ◽  
Donato Di Venere ◽  
Stefania Mardente ◽  
Stefania Miccadei
Keyword(s):  
Breast Cancer ◽  
Synergistic Effect ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Combined Treatment ◽  
Breast Cancer Cell Lines ◽  
Chemotherapeutic Drugs ◽  
Flap Endonuclease 1

Combined treatment of several natural polyphenols and chemotherapeutic agents is more effective comparing to the drug alone in inhibiting cancer cell growth. Polyphenolic artichoke extracts (AEs) have been shown to have anticancer properties by triggering apoptosis or reactive oxygen species- (ROS-) mediated senescence when used at high or low doses, respectively. Our aim was to explore the chemosensitizing potential of AEs in order to enhance the efficacy of conventional chemotherapy in breast cancer cells. We employed breast cancer cell lines to assess the potential synergistic effect of a combined treatment of AEs/paclitaxel (PTX) or AEs/adriamycin (ADR) and to determine the underlying mechanisms correlated to this potential therapeutic approach. Our data shows that AEs/PTX reduced cell proliferation by increasing DNA damage response (DDR) mediated by Flap endonuclease 1 (FEN1) downregulation that results into enhanced breast cancer cell sensitivity to chemotherapeutic drugs. We demonstrated that ROS/Nrf2 and p-ERK pathways are two molecular mechanisms involved in the synergistic effect of AEs plus PTX treatment. To highlight the role of ROS herein, we report that the addition of antioxidant N-acetylcysteine (NAC) significantly decreased the antiproliferative effect of the combined treatment. A combined therapy could be able to reduce the dose of chemotherapeutic drugs, minimizing toxicity and side effects. Our results suggest the use of artichoke polyphenols as ROS-mediated sensitizers of chemotherapy paving the way for innovative and promising natural compound-based therapeutic strategies in oncology.

Sign in / Sign up

Export Citation Format

Share Document