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Epigenetics Linked to Resistance for Anti-Cancer Drug

Mehrdad Ghavifekr Fakhr, Kolsoum Rezaie Kahkhaie, Dariush Shanehbandi, Majid Farshdousti Hagh, Habib Zarredar, Elham Safarzadeh, Mina Abdolrahimi Vind, Behzad Baradaran
Background: In many cases of breast cancer, the aberrant methylation of TP53 gene leads to uncontrolled cell proliferation and apoptosis inhibition. Moreover, expression of oncogenes which are under the control of P53 protein could be altered. Survivin as a conspicuous example of this category plays important roles in tumorigenesis, drug resistance and apoptosis inhibition. The present study was done to reveal the effects of Scrophularia atropatana extract on epigenetic situation of TP53 gene promoter and the expression levels of anti-apoptotic gene, survivin and its potential for production of cancer epi-drugs...
September 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Mahbuba Rahman, Mohammad Rubayet Hasan
Metabolic alterations, driven by genetic and epigenetic factors, have long been known to be associated with the etiology of cancer. Furthermore, accumulating evidence suggest that cancer metabolism is intimately linked to drug resistance, which is currently one of the most important challenges in cancer treatment. Altered metabolic pathways help cancer cells to proliferate at a rate higher than normal, adapt to nutrient limited conditions, and develop drug resistance phenotypes. Application of systems biology, boosted by recent advancement of novel high-throughput technologies to obtain cancer-associated, transcriptomic, proteomic and metabolomic data, is expected to make a significant contribution to our understanding of metabolic properties related to malignancy...
2015: Metabolites
Patrycja Czerwinska, Bozena Kaminska
Cancer stem cells (CSCs) are rare, tumour-initiating cells that exhibit stem cell properties: capacity of self-renewal, pluripotency, highly tumorigenic potential, and resistance to therapy. Cancer stem cells have been characterised and isolated from many cancers, including breast cancer. Developmental pathways, such as the Wnt/β-catenin, Notch/γ-secretase/Jagged, Shh (sonic hedgehog), and BMP signalling pathways, which direct proliferation and differentiation of normal stem cells, have emerged as major signalling pathways that contribute to the self-renewal of stem and/or progenitor cells in a variety of organs and cancers...
2015: Contemporary Oncology Współczesna Onkologia
Valentina Zuco, Giuliana Cassinelli, Giacomo Cossa, Laura Gatti, Enrica Favini, Monica Tortoreto, Denis Cominetti, Eugenio Scanziani, Vittoria Castiglioni, Raffaella Cincinelli, Giuseppe Giannini, Franco Zunino, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Non-Small Cell Lung Cancer (NSCLC) remains an aggressive and fatal disease with low responsiveness to chemotherapy, frequent drug resistance development and metastatic behavior. Platinum-based therapy is the standard of care for NSCLC with limited benefits. Since epigenetic alterations have been implicated in the aggressive behavior of lung cancer, the purpose of the present study was to examine the capability of the pan-histone deacetylase inhibitor SAHA and of ST3595, a novel hydroxamate-based compound, to interfere with the proliferative and invasive potential of NSCLC cells...
March 15, 2015: Biochemical Pharmacology
Daniel Ansari, Carlos Urey, Katarzyna Said Hilmersson, Monika P Bauden, Fredrik Ek, Roger Olsson, Roland Andersson
BACKGROUND/AIM: Mucin 4 (MUC4) has been linked to resistance to gemcitabine in pancreatic cancer cells. The aim of the present study was to assess whether epigenetic control of MUC4 expression can sensitize pancreatic cancer cells to gemcitabine treatment. MATERIALS AND METHODS: A 76-member combined epigenetics and phosphatase small-molecule inhibitor library was screened for anti-proliferative activity against the MUC4(+) gemcitabine-resistant pancreatic cancer cell line Capan-1, followed by high-content screening of protein expression...
October 2014: Anticancer Research
Natalie E Simpson, Volodymyr P Tryndyak, Marta Pogribna, Frederick A Beland, Igor P Pogribny
The interplay of metabolism and epigenetic regulatory mechanisms has become a focal point for a better understanding of cancer development and progression. In this study, we have acquired data supporting previous observations that demonstrate glutamine metabolism affects histone modifications in human breast cancer cell lines. Treatment of non-invasive epithelial (T-47D and MDA-MB-361) and invasive mesenchymal (MDA-MB-231 and Hs-578T) breast cancer cell lines with the glutaminase inhibitor, Compound 968, resulted in cytotoxicity in all cell lines, with the greatest effect being observed in MDA-MB-231 breast cancer cells...
December 1, 2012: Epigenetics: Official Journal of the DNA Methylation Society
Hiroto Yamazaki, C Wilson Xu, Motohiko Naito, Hiroko Nishida, Toshihiro Okamoto, Farhana Ishrat Ghani, Satoshi Iwata, Takeshi Inukai, Kanji Sugita, Chikao Morimoto
Although the prognosis of acute lymphoblastic leukemia (ALL) has improved considerably in recent years, some of the cases still exhibit therapy-resistant. We have previously reported that CD9 was expressed heterogeneously in B-ALL cell lines and CD9(+) cells exhibited an asymmetric cell division with greater tumorigenic potential than CD9(-) cells. CD9(+) cells were also serially transplantable in immunodeficient mice, indicating that CD9(+) cell possess self-renewal capacity. In the current study, we performed more detailed analysis of CD9 function for the cancer stem cell (CSC) properties...
May 27, 2011: Biochemical and Biophysical Research Communications
Qin Yan, Narendra Wajapeyee
Human cancer can arise due to inherited and sporadic genetic and epigenetic changes. These changes consequently inhibit the function of tumor suppressors and pro-apoptotic genes, while activate oncogenes. Most human cancers arise as benign tumors; after acquiring additional genetic and epigenetic changes, they become malignant and eventually metastasize to distal organs. Recent studies have implicated multiple tumor suppressing mechanisms that prevent neoplastic transformation and thus have anti-cancer activities...
February 2010: Cancer Biology & Therapy
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