scholarly journals The cyclin-dependent kinase inhibitor roscovitine and the nucleoside analog sangivamycin induce apoptosis in caspase-3 deficient breast cancer cells independent of caspase mediated P-glycoprotein cleavage: Implications for therapy of drug resistant breast cancers

Cell Cycle ◽  
2009 ◽  
Vol 8 (9) ◽  
pp. 1421-1425 ◽  
Author(s):  
Alessandra Cappellini ◽  
Francesca Chiarini ◽  
Andrea Ognibene ◽  
James A. McCubrey ◽  
Alberto M. Martelli
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Caspase 3 ◽  
Kinase Inhibitor ◽  
Drug Resistant ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
P Glycoprotein

scholarly journals Estrogen-mediated epigenetic repression of the imprinted gene cyclin-dependent kinase inhibitor 1C in breast cancer cells

2011 ◽  
Vol 32 (6) ◽  
pp. 812-821 ◽  
Author(s):  
Benjamin A.T. Rodriguez ◽  
Yu-I Weng ◽  
Ta-Ming Liu ◽  
Tao Zuo ◽  
Pei-Yin Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Imprinted Gene ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Epigenetic Repression

scholarly journals Photostable and Biocompatible Fluorescent Silicon Nanoparticles for Imaging-Guided Co-Delivery of siRNA and Doxorubicin to Drug-Resistant Cancer Cells

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Daoxia Guo ◽  
Xiaoyuan Ji ◽  
Fei Peng ◽  
Yiling Zhong ◽  
Binbin Chu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Interference ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Silicon Nanoparticles ◽  
Multidrug Resistant ◽  
Rnase A ◽  
Drug Resistant ◽  
Fluorescent Silicon Nanoparticles ◽  
P Glycoprotein

Abstract The development of effective and safe vehicles to deliver small interfering RNA (siRNA) and chemotherapeutics remains a major challenge in RNA interference-based combination therapy with chemotherapeutics, which has emerged as a powerful platform to treat drug-resistant cancer cells. Herein, we describe the development of novel all-in-one fluorescent silicon nanoparticles (SiNPs)-based nanomedicine platform for imaging-guided co-delivery of siRNA and doxorubicin (DOX). This approach enhanced therapeutic efficacy in multidrug-resistant breast cancer cells (i.e., MCF-7/ADR cells). Typically, the SiNP-based nanocarriers enhanced the stability of siRNA in a biological environment (i.e., medium or RNase A) and imparted the responsive release behavior of siRNA, resulting in approximately 80% down-regulation of P-glycoprotein expression. Co-delivery of P-glycoprotein siRNA and DOX led to > 35-fold decrease in the half maximal inhibitory concentration of DOX in comparison with free DOX, indicating the pronounced therapeutic efficiency of the resultant nanocomposites for drug-resistant breast cancer cells. The intracellular time-dependent release behaviors of siRNA and DOX were revealed through tracking the strong and stable fluorescence of SiNPs. These data provide valuable information for designing effective RNA interference-based co-delivery carriers.

scholarly journals Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition

2021 ◽  
Vol 22 (17) ◽  
pp. 9243
Author(s):  
Mashan L. Abdullah ◽  
Othman Al-Shabanah ◽  
Zeinab K. Hassan ◽  
Mohamed M. Hafez
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Expression Levels ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Gene And Protein Expression ◽  
Anti Cancer

The use of natural compounds is promising in approaches to prevent and treat cancer. The long-term application of most currently employed chemotherapy techniques has toxic side effects. Eugenol, a phenolic phytochemical extracted from certain essential oils, has an anti-cancer effect. The modulation of autophagy can promote either the survival or apoptosis of cancer cells. Triple-negative (MDA-MB-231) and HER2 positive (SK-BR-3) breast cancer cell lines were treated with different doses of eugenol. Apoptosis was detected by a flow-cytometry technique, while autophagy was detected by acridine orange. Real-time PCR and Western blot assays were applied to investigate the effect of eugenol on the gene and protein expression levels of autophagy and apoptotic genes. Treating cells with different concentrations of eugenol significantly inhibited cell proliferation. The protein levels of AKT serine/threonine kinase 1 (AKT), forkhead box O3 (FOXO3a), cyclin dependent kinase inhibitor 1A (p21), cyclin-dependent kinase inhibitor (p27), and Caspase-3 and -9 increased significantly in Eugenol-treated cells. Eugenol also induced autophagy by upregulating the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and downregulating the expression of nucleoporin 62 (NU p62). Eugenol is a promising natural anti-cancer agent against triple-negative and HER2-positive breast cancer. It appears to work by targeting the caspase pathway and by inducing autophagic cell death.

scholarly journals Increased autophagy blocks HER2-mediated breast tumorigenesis

2018 ◽  
Vol 115 (16) ◽  
pp. 4176-4181 ◽  
Author(s):  
Silvia Vega-Rubín-de-Celis ◽  
Zhongju Zou ◽  
Álvaro F. Fernández ◽  
Bo Ci ◽  
Min Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Inhibitor ◽  
Genetically Engineered ◽  
Beclin 1 ◽  
Allelic Loss ◽  
Breast Cancers ◽  
Her2 Positive

Allelic loss of the autophagy gene, beclin 1/BECN1, increases the risk of patients developing aggressive, including human epidermal growth factor receptor 2 (HER2)-positive, breast cancers; however, it is not known whether autophagy induction may be beneficial in preventing HER2-positive breast tumor growth. We explored the regulation of autophagy in breast cancer cells by HER2 in vitro and the effects of genetic and pharmacological strategies to increase autophagy on HER2-driven breast cancer growth in vivo. Our findings demonstrate that HER2 interacts with Beclin 1 in breast cancer cells and inhibits autophagy. Mice with increased basal autophagy due to a genetically engineered mutation in Becn1 are protected from HER2-driven mammary tumorigenesis, and HER2 fails to inhibit autophagy in primary cells derived from these mice. Moreover, treatment of mice with HER2-positive human breast cancer xenografts with the Tat-Beclin 1 autophagy-inducing peptide inhibits tumor growth as effectively as a clinically used HER2 tyrosine kinase inhibitor (TKI). This inhibition of tumor growth is associated with a robust induction of autophagy, a disruption of HER2/Beclin 1 binding, and a transcriptional signature in the tumors distinct from that observed with HER2 TKI treatment. Taken together, these findings indicate that the HER2-mediated inhibition of Beclin 1 and autophagy likely contributes to HER2-mediated tumorigenesis and that strategies to block HER2/Beclin 1 binding and/or increase autophagy may represent a new therapeutic approach for HER2-positive breast cancers.

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