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https://www.readbyqxmd.com/read/28534825/a-novel-combination-of-withaferin-a-and-sulforaphane-inhibits-epigenetic-machinery-cellular-viability-and-induces-apoptosis-of-breast-cancer-cells
#1
Kendra J Royston, Neha Udayakumar, Kayla Lewis, Trygve O Tollefsbol
With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534508/utx-promotes-hormonally-responsive-breast-carcinogenesis-through-feed-forward-transcription-regulation-with-estrogen-receptor
#2
G Xie, X Liu, Y Zhang, W Li, S Liu, Z Chen, B Xu, J Yang, L He, Z Zhang, T Jin, X Yi, L Sun, Y Shang, J Liang
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28532420/going-beyond-genetics-to-discover-cancer-targets
#3
Gabriel J Sandoval, William C Hahn
Two recent studies demonstrate the power of integrating tumor genotype information with epigenetic and proteomic studies to discover potential therapeutic targets in breast cancer.
May 22, 2017: Genome Biology
https://www.readbyqxmd.com/read/28505145/dna-methylation-targets-influenced-by-bisphenol-a-and-or-genistein-are-associated-with-survival-outcomes-in-breast-cancer-patients
#4
Rohit R Jadhav, Julia Santucci-Pereira, Yao V Wang, Joseph Liu, Theresa D Nguyen, Jun Wang, Sarah Jenkins, Jose Russo, Tim H-M Huang, Victor X Jin, Coral A Lamartiniere
Early postnatal exposures to Bisphenol A (BPA) and genistein (GEN) have been reported to predispose for and against mammary cancer, respectively, in adult rats. Since the changes in cancer susceptibility occurs in the absence of the original chemical exposure, we have investigated the potential of epigenetics to account for these changes. DNA methylation studies reveal that prepubertal BPA exposure alters signaling pathways that contribute to carcinogenesis. Prepubertal exposure to GEN and BPA + GEN revealed pathways involved in maintenance of cellular function, indicating that the presence of GEN either reduces or counters some of the alterations caused by the carcinogenic properties of BPA...
May 15, 2017: Genes
https://www.readbyqxmd.com/read/28503860/epigenetic-silencing-of-adamts18-promotes-cell-migration-and-invasion-of-breast-cancer-through-akt-and-nf-%C3%AE%C2%BAb-signaling
#5
Hongying Xu, Qian Xiao, Yu Fan, Tingxiu Xiang, Chen Li, Chunhong Li, Shuman Li, Tianli Hui, Lu Zhang, Hongzhong Li, Lili Li, Guosheng Ren
ADAMTS18 dysregulation plays an important role in many disease processes including cancer. We previously found ADAMTS18 as frequently methylated tumor suppressor gene (TSG) for multiple carcinomas, however, its biological functions and underlying molecular mechanisms in breast carcinogenesis remain unknown. Here, we found that ADAMTS18 was silenced or downregulated in breast cancer cell lines. ADAMTS18 was reduced in primary breast tumor tissues as compared with their adjacent noncancer tissues. ADAMTS18 promoter methylation was detected in 70...
May 15, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28489652/histone-deacetylase-inhibitors-enhance-cytotoxicity-towards-breast-tumors-while-preserving-the-wound-healing-function-of-adipose-derived-stem-cells
#6
Kiavash R Koko, Shaohua Chang, Ashleigh L Hagaman, Marc W Fromer, Ryan S Nolan, John P Gaughan, Ping Zhang, Jeffrey P Carpenter, Spencer A Brown, Martha Matthews, Dorothy Bird
INTRODUCTION: Paclitaxel improves the oncologic response of breast cancer resections; however, it may negatively affect the wound-healing potential of human adipose-derived stem cells (hASCs) for fat grafting and reconstructive surgery. Histone deacetylase inhibitors (HDACis) modify the epigenetic regulation of gene expression and stabilize microtubules similarly to paclitaxel, thus, creating a synergistic mechanism of cell cycle arrest. We aim to combine these drugs to enhance cytotoxicity towards breast cancer cells, while preserving the wound-healing function of hASCs for downstream reconstructive applications...
June 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28487351/gestational-high-fat-diet-and-bisphenol-a-exposure-heightens-mammary-cancer-risk
#7
Yuet-Kin Leung, Vinothini Govindarajah, Ana Cheong, Jen Veevers, Dan Song, Robin Gear, Xuegong Zhu, Jun Ying, Ady Kendler, Mario Medvedovic, Scott Belcher, Shuk-Mei Ho
In utero exposure to bisphenol A (BPA) increases mammary cancer susceptibility in offspring. High fat diet is widely believed to be a risk factor of breast cancer. The objective of this study was to determine whether maternal exposure to BPA in addition to high-butterfat (HBF) intake during pregnancy further impacts carcinogen-induced mammary cancer risk in offspring, and its dose-response curve. In this study, we found that gestational HBF intake in addition to a low-dose BPA (25 µg/kg BW/day) exposure increased mammary tumor incidence in a 50-day-of-age chemical carcinogen administration model and altered mammary gland morphology in offspring in a non-monotonic manner, while shortening tumor-free survival time compared with the HBF-alone group...
May 9, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28486273/zebularine-treatment-induces-mage-a11-expression-and-improves-ctl-cytotoxicity-using-a-novel-identified-hla-a2-restricted-mage-a11-peptide
#8
Jiandong Zhang, Meixiang Sang, Lina Gu, Fei Liu, Weijing Li, Danjing Yin, Yunyan Wu, Shina Liu, Weina Huang, Baoen Shan
Melanoma-associated antigen-A11 (MAGE-A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE-A11 is a potential immunotherapy target in breast cancer. MAGE-A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of MAGE-A11 expression is crucial for the recognition and killing of breast cancer cells by cytotoxic T lymphocytes (CTL). In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested...
May 8, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28486103/tackling-resistance-to-pi3k-inhibition-by-targeting-the-epigenome
#9
Shany Koren, Mohamed Bentires-Alj
Phosphoinositide-3-kinase (PI3K) pathway inhibitors have emerged as promising therapeutic agents for estrogen receptor (ERα)-positive breast cancers. However, incipient resistance limits the clinical benefit. Toska and colleagues identified that the epigenetic regulator KMT2D enhances ERα activity in BYL719-treated PIK3CA mutant breast cancer, leading to a rationale for targeting the epigenome and PI3K signaling.
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28481734/hlj1-dnajb4-gene-is-a-novel-biomarker-candidate-in-breast-cancer
#10
Tolga Acun, Natalie Doberstein, Jens K Habermann, Timo Gemoll, Christoph Thorns, Emin Oztas, Thomas Ried
Breast cancer is the most common cancer type and cause of cancer-related mortality among women worldwide. New biomarker discovery is crucial for diagnostic innovation and personalized medicine in breast cancer. Heat shock proteins (HSPs) have been increasingly reported as biomarkers and potential drug targets for cancers. HLJ1 (DNAJB4) belongs to the DNAJ (HSP40) family of HSPs and is regarded as a tumor suppressor gene in lung, colon, and gastric cancers. However, the role of the HLJ1 gene in breast cancer is currently unknown...
May 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28473774/lncrna-six1-encodes-a-micropeptide-to-activate-six1-in-cis-and-is-involved-in-cell-proliferation-and-muscle-growth
#11
Bolin Cai, Zhenhui Li, Manting Ma, Zhijun Wang, Peigong Han, Bahareldin A Abdalla, Qinghua Nie, Xiquan Zhang
Long non-coding RNAs (lncRNAs) play important roles in epigenetic regulation of skeletal muscle development. In our previous RNA-seq study (accession number GSE58755), we found that lncRNA-Six1 is an lncRNA that is differentially expressed between White Recessive Rock (WRR) and Xinghua (XH) chicken. In this study, we have further demonstrated that lncRNA-Six1 is located 432 bp upstream of the gene encoding the protein Six homeobox 1 (Six1). A dual-luciferase reporter assay identified that lncRNA-Six1 overlaps the Six1 proximal promoter...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28467815/epigenetic-silencing-of-triple-negative-breast-cancer-hallmarks-by-withaferin-a
#12
Katarzyna Szarc Vel Szic, Ken Declerck, René A J Crans, Jolien Diddens, David B Scherf, Clarissa Gerhäuser, Wim Vanden Berghe
Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3)...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467790/the-synthetic-antihyperlipidemic-drug-potassium-piperate-selectively-kills-breast-cancer-cells-through-inhibiting-g1-s-phase-transition-and-inducing-apoptosis
#13
Lifei Fan, Xuemin Cao, Huijuan Yan, Qian Wang, Xiaoxia Tian, Lan Zhang, Xiaoyan He, Gereltu Borjihan, Morigen Morigen
Piper longum L. is a well-known traditional antihyperlipidemic medicine in China, containing medicinal constituents of piperine, pipernonaline and piperlonguminine in its fruit. However, the antitumor properties of these constituents have not yet been studied. We found that potassium piperate (GBK), a derivative of piperine, inhibited proliferation of cancer cells. GBK selectively inhibited the G1-S-phase transition in breast cancer cells and the G1 arrest was correlated with induction of p27 expression, which is an inhibitor for cyclin-dependent kinases, and inhibition of cyclin A, cyclin E and cyclin B expression...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454353/prmt8-demonstrates-variant-specific-expression-in-cancer-cells-and-correlates-with-patient-survival-in-breast-ovarian-and-gastric-cancer
#14
Sarah J Hernandez, David M Dolivo, Tanja Dominko
Recent emphasis has been placed on the role of epigenetic regulators and epigenetic marks as biomarkers for cancer diagnosis and prognosis, and as therapeutic targets for treatment. One such class of regulators is the protein arginine methyltransferase (PRMT) family. The present study examined available curated data regarding the expression and alteration of one of the least studied PRMT family members, PRMT8, in various types of cancer and cancer cell lines. Publicly available cancer data on PRMT8 expression were examined using the Human Protein Atlas and the Kaplan-Meier Plotter, and reverse transcription-polymerase chain reaction was used to screen a selection of human cell lines for variant-specific PRMT8 expression...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454214/genome-wide-analysis-of-gynecologic-cancer-the-cancer-genome-atlas-in-ovarian-and-endometrial-cancer
#15
Moito Iijima, Kouji Banno, Ryuichiro Okawa, Megumi Yanokura, Miho Iida, Takashi Takeda, Haruko Kunitomi-Irie, Masataka Adachi, Kanako Nakamura, Kiyoko Umene, Yuya Nogami, Kenta Masuda, Eiichiro Tominaga, Daisuke Aoki
Cancer typically develops due to genetic abnormalities, but a single gene abnormality cannot completely account for the onset of cancer. The Cancer Genome Atlas (CGA) project was conducted for the cross-sectional genome-wide analysis of numerous genetic abnormalities in various types of cancer. This approach has facilitated the identification of novel AT-rich interaction domain 1A gene mutations in ovarian clear cell carcinoma, frequent tumor protein 53 (TP53) gene mutations in high-grade ovarian serous carcinoma, and Kirsten rat sarcoma and B-rapidly accelerated fibrosarcoma proto-oncogene, serine/threonine kinase gene mutations in low-grade ovarian serous carcinoma...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453505/breast-cancer-intra-tumor-heterogeneity-one-tumor-different-entities
#16
José Esparza-López, Elizabet Escobar-Arriaga, Santos Soto-Germes, María de Jesús Ibarra-Sánchez
In recent years, it has become evident that intra-tumor heterogeneity of breast cancer is a big challenge for the diagnosis, treatment, and clinical course of tumor-bearing patients. The advances in molecular biology and other technologies have led to the knowledge that a breast cancer tumor is comprised of multiple cellular entities. Here we review the two theories that have been described, trying to explain the origin of intra-tumor heterogeneity: clonal evolution and cancer stem cells. The first one considers that a single cell gives rise to many subpopulations through the accumulation of multiple aberrations, while the cancer stem cells theory foresees a hierarchical tumor evolution where only a few cells with self-renewal capacity give rise to different subpopulations...
March 2017: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/28443466/promoter-methylation-and-gene-polymorphism-are-two-independent-events-in-regulation-of-gstp1-gene-expression
#17
Aaliya Bhat, A Masood, K A Wani, Younus Ahmad Bhat, Bushra Nissar, Nuzhat Shaheen Khan, B A Ganai
Breast carcinogenesis is a multistep process, involving both genetic and epigenetic modification process of genes, involved in diverse pathways ranging from DNA repair to metabolic processes. This study was undertaken to assess the role of promoter methylation of GSTP1 gene, a member of glutathione-S-transferase family of enzymes, in relation to its expression, polymorphism, and clinicopathological parameters. Tissue samples were taken from breast cancer patients and paired with their normal adjacent tissues...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28434943/epigenetic-pathways-in-human-disease-the-impact-of-dna-methylation-on-stress-related-pathogenesis-and-current-challenges-in-biomarker-development
#18
M Austin Argentieri, Sairaman Nagarajan, Bobak Seddighzadeh, Andrea A Baccarelli, Alexandra E Shields
HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11β1/2 genes in adults...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28432260/dual-histone-reader-zmynd8-inhibits-cancer-cell-invasion-by-positively-regulating-epithelial-genes
#19
Moitri Basu, Isha Sengupta, Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy, Chandrima Das
Enhanced migratory potential and invasiveness of cancer cells attribute crucially.in cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed as chromatin reader. ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a key component of transcription regulatory network, has been recently shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28431263/epigenetic-therapy-and-chemosensitization-in-solid-malignancy
#20
REVIEW
Sean M Ronnekleiv-Kelly, Anup Sharma, Nita Ahuja
Epigenetic modifications result in dynamic shifts between transcriptionally active and suppressed states. The potentially reversible nature of epigenetic changes underlies the concept of epigenetic therapy, which serves to reprogram cancer cells as opposed to inducing cytotoxicity that occurs with standard chemotherapeutics. There are numerous enzymes involved in epigenetic changes and each can be potentially targetable. Although many investigations have evaluated the clinical potential of the various epigenetic therapies, currently only histone deacetylase inhibitors and DNA methyltransferase inhibitors are approved for use in specific hematologic malignancies...
April 8, 2017: Cancer Treatment Reviews
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