In three human breast cancer cell lines, we demonstrated that Akt-mTOR-eEF-2K pathway was involved in TBMS1-induced activation of autophagy, while Akt-mediated downregulations of Mcl-1, Bcl-xl, and Bcl-2 led to the activation of apoptosis of the breast cancer cells.
We also found that pectolinarigenin inhibited breast cancer cell proliferation and induced apoptosis <i>via</i> mitochondrial-related apoptosis pathway, reduced mitochondrial membrane potential and the expression of Bcl-2, increased expression of Bax, and cleaved caspase-3 as well as disturbed the ROS generation.
The regulation of BCL2 was mainly associated with methylation across the molecular subtypes of breast cancer, and luminal A and luminal B subtypes showed upregulated expression of BCL2 protein, mRNA, and hypomethylation.
Because BCL2 proteins are overexpressed in breast cancer and targetable by selective antagonists, we here analysed the effect of BCL2 and BCL(X)L selective inhibitors, Venetoclax and WEHI-539, on mitochondrial bioenergetics and cell death.
All single- and combined-treated groups showed a significant increase in apoptosis (indicated by upregulated mRNA level of the pro-apoptotic marker Bax and downregulated mRNA level of the anti-apoptotic marker Bcl2) and a significant decrease in mRNA level of the two breast cancer related receptors EGFR and ERα, with the best effect in combined groups especially that contained the 4 compounds, as compared to vehicle-treated group.
The aim of this study was to examine the influence of intra-tumoral heterogeneity as well as inter-observer variability on the evaluation of various IHC markers with potential prognostic impact in breast cancer (BCL2, E-cadherin, EGFR, EMMPRIN and Ki-67).
In conclusion, rcdtB treatment inhibited tumor growth and induced apoptosis through inhibiting Bcl-2 expression, inflammatory responses, and activating C-erbB-2 and Cox-2 expression in breast cancer mouse model.
The effects of LCA on breast cancer-derived MCF-7 and MDA-MB-231 cells were studied using MTT viability assays, Annexin-FITC and Akt phosphorylation assays to evaluate anti-proliferative and pro-apoptotic properties, qRT-PCR and Western blotting assays to assess the expression of the bile acid receptor TGR5 and the estrogen receptor ERα, and genes and proteins involved in apoptosis (Bax, Bcl-2, p53) and lipogenesis (SREBP-1c, FASN, ACACA).
Activation of STAT3 and Bcl-2 and reduction of reactive oxygen species (ROS) promote radioresistance in breast cancer and overcome of radioresistance with niclosamide.
Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data.
We also performed a correlation analysis between expression levels of the 13 miRNAs and 5 cancer-associated genes, namely RASSF1(A), CHL1, APAF1, DAPK1, and BCL2, which were predicted as targets for these miRNAs, to investigate the impact of these miRNAs on these genes with key cellular functions in BC.
Two miRNAs, hsa-miR-17-5p and hsa-miR-16-5p, were identified as having the highest associations with targeted mRNAs [such as B-cell lymphoma 2 (BCL2), small body size/mothers against decapentaplegic 3 (SMAD3) and suppressor of cytokine signaling 1 (SOCS1)] and pathways associated with epithelial-mesenchymal transitions and other processes linked with cancer metastasis (including cell cycle, adherence junctions and extracellular matrix-receptor interaction). mRNAs for two genes [HECT, UBA and WWE domain containing 1 (HUWE1) and BCL2] were found to have the highest associations with miRNAs, which were down-regulated in brain metastasis specimens of breast cancer.
Importantly, this delivery strategy achieved greater knockdown of the Bcl-2 protein when compared to the leading commercial siRNA delivery system Lipofectamine® RNAiMAX, suggesting its potential utility for the targeted treatment of Bcl-2 overexpressing breast cancers.
These results demonstrate that breast cancers rapidly deploy Mcl-1 to promote cell survival, particularly when challenged with blockade of other Bcl-2 family members, warranting the continued development of Mcl-1-selective inhibitors for targeted tumor cell killing.<b>Implications:</b> Mcl-1 levels predict breast cancer response to inhibitors targeting other Bcl-2 family members, and demonstrate the key role played by Mcl-1 in resistance to this drug class.<i></i>.
The <i>N</i>-hexane extract of the marine sponge <i>Hyrtios erectus</i>, collected from North Bay, South Andaman Sea, India, showed potential antiproliferative and proapoptotic properties against a breast adenocarcinoma cell line (MCF-7).The sponge extract retarded the growth of breast carcinoma cell line MCF-7 cells in a time- and dose-dependent manner.The sponge extract induced apoptosis of breast cancer cell line MCF-7 and arrested cells in G<sub>2</sub>/M phase.The sponge extract induced downregulation of Bcl-2 protein in MCF-7 cell line and upregulation of Bax, caspase-3, and cleaved PARP.
Mechanistic studies revealed that CCL28 mediated intracellular activation of the mitogen-activated protein kinase (MAPK) signaling pathway to promote breast cancer cell proliferation and metastasis by upregulating anti-apoptotic protein Bcl-2 and suppressing cell adhesion protein β-catenin.