scholarly journals The 3,4-Quinones of Estrone and Estradiol Are the Initiators of Cancer whereas Resveratrol and N-acetylcysteine Are the Preventers

2021 ◽  
Vol 22 (15) ◽  
pp. 8238
Author(s):  
Ercole Cavalieri ◽  
Eleanor Rogan
Keyword(s):  
Breast Cancer ◽  
Dna Adducts ◽  
Mammalian Cells ◽  
Human Subjects ◽  
Test Tube ◽  
Common Mechanism ◽  
Cancer Initiation ◽  
Different Types ◽  
Catechol Estrogen ◽  
Potential Cancer

This article reviews evidence suggesting that a common mechanism of initiation leads to the development of many prevalent types of cancer. Endogenous estrogens, in the form of catechol estrogen-3,4-quinones, play a central role in this pathway of cancer initiation. The catechol estrogen-3,4-quinones react with specific purine bases in DNA to form depurinating estrogen-DNA adducts that generate apurinic sites. The apurinic sites can then lead to cancer-causing mutations. The process of cancer initiation has been demonstrated using results from test tube reactions, cultured mammalian cells, and human subjects. Increased amounts of estrogen-DNA adducts are found not only in people with several different types of cancer but also in women at high risk for breast cancer, indicating that the formation of adducts is on the pathway to cancer initiation. Two compounds, resveratrol, and N-acetylcysteine, are particularly good at preventing the formation of estrogen-DNA adducts in humans and are, thus, potential cancer-prevention compounds.

scholarly journals Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1021
Author(s):  
Carla Abrahamian ◽  
Christian Grimm
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Convincing Evidence ◽  
Signaling Cascades ◽  
Cation Channels ◽  
Pore Channel ◽  
Different Types ◽  
Canonical Wnt ◽  
The Relationship

Microphthalmia-associated transcription factor (MITF) is the principal transcription factor regulating pivotal processes in melanoma cell development, growth, survival, proliferation, differentiation and invasion. In recent years, convincing evidence has been provided attesting key roles of endolysosomal cation channels, specifically TPCs and TRPMLs, in cancer, including breast cancer, glioblastoma, bladder cancer, hepatocellular carcinoma and melanoma. In this review, we provide a gene expression profile of these channels in different types of cancers and decipher their roles, in particular the roles of two-pore channel 2 (TPC2) and TRPML1 in melanocytes and melanoma. We specifically discuss the signaling cascades regulating MITF and the relationship between endolysosomal cation channels, MAPK, canonical Wnt/GSK3 pathways and MITF.

scholarly journals A Novel Signature of CCNF-Associated E3 Ligases Collaborate and Counter Each Other in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2873
Author(s):  
Shu-Chun Chang ◽  
Chin-Sheng Hung ◽  
Bo-Xiang Zhang ◽  
Tsung-Han Hsieh ◽  
Wayne Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Mrna Level ◽  
Breast Carcinogenesis ◽  
E3 Ligases ◽  
Anti Cancer ◽  
Cancer Initiation ◽  
Cell Progression ◽  
F Box Protein ◽  
Cancer Activity

Breast cancer (BRCA) malignancy causes major fatalities amongst women worldwide. SCF (Skp1-cullin-F-box proteins) E3 ubiquitin ligases are the most well-known members of the ubiquitination–proteasome system (UPS), which promotes cancer initiation and progression. Recently, we demonstrated that FBXL8, a novel F-box protein (SCFF-boxes) of SCF E3 ligase, accelerates BRCA advancement and metastasis. Since SCFF-boxes is a key component of E3 ligases, we hypothesized that other SCFF-boxes besides FBXL8 probably collaborate in regulating breast carcinogenesis. In this study, we retrospectively profiled the transcriptome of BRCA tissues and found a notable upregulation of four SCFF-box E3 ligases (FBXL8, FBXO43, FBXO15, and CCNF) in the carcinoma tissues. Similar to FBXL8, the knockdown of FBXO43 reduced cancer cell viability and proliferation, suggesting its pro-tumorigenic role. The overexpression of CCNF inhibited cancer cell progression, indicating its anti-tumorigenic role. Unexpectedly, CCNF protein was markedly downregulated in BRCA tissues, although its mRNA level was high. We showed that both E3 ligases, FBXL8 and FZR1, pulled down CCNF. Double knockdown of FBXL8 and FZR1 caused CCNF accumulation. On the other hand, CCNF itself pulled down a tumorigenic factor, RRM2, and CCNF overexpression reduced RRM2. Altogether, we propose a signature network of E3 ligases that collaboratively modulates CCNF anti-cancer activity. There is potential to target BRCA through modulation of the partnership axes of (i) CCNF-FBXL8, (ii) CCNF-FZR1, and (iii) CCNF-RRM2, particularly, via CCNF overexpression and activation and FBXL8/FZR1 suppression.

scholarly journals Nongenotoxic ABCB1 activator tetraphenylphosphonium can contribute to doxorubicin resistance in MX-1 breast cancer cell line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raimonda Kubiliute ◽  
Indre Januskeviciene ◽  
Ruta Urbanaviciute ◽  
Kristina Daniunaite ◽  
Monika Drobniene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Protein Level ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Common Mechanism ◽  
Dna Hypomethylation ◽  
Mesenchymal Transition ◽  
Molecular Features

AbstractHyperactivation of ABC transporter ABCB1 and induction of epithelial–mesenchymal transition (EMT) are the most common mechanism of acquired cancer chemoresistance. This study describes possible mechanisms, that might contribute to upregulation of ABCB1 and synergistically boost the acquisition of doxorubicin (DOX) resistance in breast cancer MX-1 cell line. DOX resistance in MX-1 cell line was induced by a stepwise increase of drug concentration or by pretreatment of cells with an ABCB1 transporter activator tetraphenylphosphonium (TPP+) followed by DOX exposure. Transcriptome analysis of derived cells was performed by human gene expression microarrays and by quantitative PCR. Genetic and epigenetic mechanisms of ABCB1 regulation were evaluated by pyrosequencing and gene copy number variation analysis. Gradual activation of canonical EMT transcription factors with later activation of ABCB1 at the transcript level was observed in DOX-only treated cells, while TPP+ exposure induced considerable activation of ABCB1 at both, mRNA and protein level. The changes in ABCB1 mRNA and protein level were related to the promoter DNA hypomethylation and the increase in gene copy number. ABCB1-active cells were highly resistant to DOX and showed morphological and molecular features of EMT. The study suggests that nongenotoxic ABCB1 inducer can possibly accelerate development of DOX resistance.

scholarly journals New insights on CRISPR/Cas9-based therapy for breast Cancer

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Hussein Sabit ◽  
Shaimaa Abdel-Ghany ◽  
Huseyin Tombuloglu ◽  
Emre Cevik ◽  
Amany Alqosaibi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Research ◽  
Animal Models ◽  
Human Cancer ◽  
Step Process ◽  
Cancer Initiation ◽  
Malignant State ◽  
Treat Breast Cancer

AbstractCRISPR/Cas9 has revolutionized genome-editing techniques in various biological fields including human cancer research. Cancer is a multi-step process that encompasses the accumulation of mutations that result in the hallmark of the malignant state. The goal of cancer research is to identify these mutations and correlate them with the underlying tumorigenic process. Using CRISPR/Cas9 tool, specific mutations responsible for cancer initiation and/or progression could be corrected at least in animal models as a first step towards translational applications. In the present article, we review various novel strategies that employed CRISPR/Cas9 to treat breast cancer in both in vitro and in vivo systems.

NEURAL CLASSIFICATION OF MASS ABNORMALITIES WITH DIFFERENT TYPES OF FEATURES IN DIGITAL MAMMOGRAPHY

2006 ◽  
Vol 06 (01) ◽  
pp. 61-75 ◽  
Author(s):  
R. PANCHAL ◽  
B. VERMA
Keyword(s):  
Breast Cancer ◽  
Research Work ◽  
Breast Cancer Diagnosis ◽  
Classification Rate ◽  
Test Dataset ◽  
Benchmark Database ◽  
Different Types ◽  
Breast Tissues ◽  
Mass Type

Early detection of breast abnormalities remains the primary prevention against breast cancer despite the advances in breast cancer diagnosis and treatment. Presence of mass in breast tissues is highly indicative of breast cancer. The research work presented in this paper investigates the significance of different types of features using proposed neural network based classification technique to classify mass type of breast abnormalities in digital mammograms into malignant and benign. 14 gray level based features, four BI-RADS features, patient age feature and subtlety value feature have been explored using the proposed research methodology to attain maximum classification on test dataset. The proposed research technique attained a 91% testing classification rate with a 100% training classification rate on digital mammograms taken from the DDSM benchmark database.

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