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 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 Differential expression of cyclin dependent kinase inhibitor 3 in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Primary Tumors ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Ductal Cells

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cyclin dependent kinase inhibitor 3, CDKN3, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CDKN3 was also differentially expressed in bulk tumor in human breast cancer (3). CDKN3 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CDKN3 in primary tumors of the breast was correlated with overall survival in patients with basal-like and luminal B type cancer, while within triple negative breast cancer, primary tumor expression of CDKN3 was correlated with distant metastasis-free survival in patients with mesenchymal stem-like subtype disease. CDKN3 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

scholarly journals Activated STAT3 Is a Novel Regulator of the XRCC1 Promoter and Selectively Increases XRCC1 Protein Levels in Triple Negative Breast Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5475
Author(s):  
Griffin Wright ◽  
Manoj Sonavane ◽  
Natalie R. Gassman
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Excision Repair ◽  
Strand Break ◽  
Xrcc1 Gene ◽  
Single Strand Break ◽  
Expression Levels ◽  
Constitutive Activation ◽  
Gene And Protein Expression

Base Excision Repair (BER) addresses base lesions and abasic sites induced by exogenous and endogenous stressors. X-ray cross complementing group 1 (XRCC1) functions as a scaffold protein in BER and single-strand break repair (SSBR), facilitating and coordinating repair through its interaction with a host of critical repair proteins. Alterations of XRCC1 protein and gene expression levels are observed in many cancers, including colorectal, ovarian, and breast cancer. While increases in the expression level of XRCC1 are reported, the transcription factors responsible for this up-regulation are not known. In this study, we identify the signal transducer and activator of transcription 3 (STAT3) as a novel regulator of XRCC1 through chromatin immunoprecipitation. Activation of STAT3 through phosphorylation at Y705 by cytokine (IL-6) signaling increases the expression of XRCC1 and the occupancy of STAT3 within the XRCC1 promoter. In triple negative breast cancer, the constitutive activation of STAT3 upregulates XRCC1 gene and protein expression levels. Increased expression of XRCC1 is associated with aggressiveness and resistance to DNA damaging chemotherapeutics. Thus, we propose that activated STAT3 regulates XRCC1 under stress and growth conditions, but constitutive activation in cancers results in dysregulation of XRCC1 and subsequently BER and SSBR.

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