scholarly journals New Perspectives of CYP1B1 Inhibitors in the Light of Molecular Studies

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 817
Author(s):  
Renata Mikstacka ◽  
Zbigniew Dutkiewicz
Keyword(s):  
Cancer Progression ◽  
Cancer Chemoprevention ◽  
Cancer Drug ◽  
Cellular Functions ◽  
Cytochrome P450 1B1 ◽  
Cancer Drug Resistance ◽  
Human Cytochrome ◽  
Anti Cancer ◽  
Endogenous Substrates ◽  
Metabolism Of Xenobiotics

Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic heme-containing monooxygenase. CYP1B1 contributes to the oxidative metabolism of xenobiotics, drugs, and endogenous substrates like melatonin, fatty acids, steroid hormones, and retinoids, which are involved in diverse critical cellular functions. CYP1B1 plays an important role in the pathogenesis of cardiovascular diseases, hormone-related cancers and is responsible for anti-cancer drug resistance. Inhibition of CYP1B1 activity is considered as an approach in cancer chemoprevention and cancer chemotherapy. CYP1B1 can activate anti-cancer prodrugs in tumor cells which display overexpression of CYP1B1 in comparison to normal cells. CYP1B1 involvement in carcinogenesis and cancer progression encourages investigation of CYP1B1 interactions with its ligands: substrates and inhibitors. Computational methods, with a simulation of molecular dynamics (MD), allow the observation of molecular interactions at the binding site of CYP1B1, which are essential in relation to the enzyme’s functions.

Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance

2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Cancer Drugs ◽  
Repair Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Cancerous Cells

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

scholarly journals Role of HDAC3-miRNA-CAGE Network in Anti-Cancer Drug-Resistance

2018 ◽  
Vol 20 (1) ◽  
pp. 51 ◽  
Author(s):  
Yoojung Kwon ◽  
Youngmi Kim ◽  
Hyun Jung ◽  
Dooil Jeoung
Keyword(s):  
Molecular Networks ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Angiogenic Potential ◽  
Histone Deacetylase 3 ◽  
Cancer Drug Resistance ◽  
Tumorigenic Potential ◽  
Anti Cancer ◽  
Cancer Testis

Histone modification is associated with resistance to anti-cancer drugs. Epigenetic modifications of histones can regulate resistance to anti-cancer drugs. It has been reported that histone deacetylase 3 (HDAC3) regulates responses to anti-cancer drugs, angiogenic potential, and tumorigenic potential of cancer cells in association with cancer-associated genes (CAGE), and in particular, a cancer/testis antigen gene. In this paper, we report the roles of microRNAs that regulate the expression of HDAC3 and CAGE involved in resistance to anti-cancer drugs and associated mechanisms. In this review, roles of HDAC3-miRNAs-CAGE molecular networks in resistance to anti-cancer drugs, and the relevance of HDAC3 as a target for developing anti-cancer drugs are discussed.

scholarly journals Development of a Cationic Amphiphilic Helical Peptidomimetic (B18L) As A Novel Anti-Cancer Drug Lead

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2448 ◽  
Author(s):  
Yuan Lyu ◽  
Steven Kopcho ◽  
Folnetti A. Alvarez ◽  
Bryson C. Okeoma ◽  
Chioma M. Okeoma
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Drug ◽  
Cancer Cell Death ◽  
Drug Lead ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Caspase Substrate ◽  
Dynamics Simulations

BST-2 is a novel driver of cancer progression whose expression confers oncogenic properties to breast cancer cells. As such, targeting BST-2 in tumors may be an effective therapeutic approach against breast cancer. Here, we sought to develop potent cytotoxic anti-cancer agent using the second-generation BST-2-based anti-adhesion peptide, B18, as backbone. To this end, we designed a series of five B18-derived peptidomimetics. Among these, B18L, a cationic amphiphilic α-helical peptidomimetic, was selected as the drug lead because it displayed superior anti-cancer activity against both drug-resistant and drug-sensitive cancer cells, with minimal toxicity on normal cells. Probing mechanism of action using molecular dynamics simulations, biochemical and membrane biophysics studies, we observed that B18L binds BST-2 and possesses membranolytic characteristics. Furthermore, molecular biology studies show that B18L dysregulates cancer signaling pathways resulting in decreased Src and Erk1/2 phosphorylation, increased expression of pro-apoptotic Bcl2 proteins, caspase 3 cleavage products, as well as processing of the caspase substrate, poly (ADP-ribose) polymerase-1 (PARP-1), to the characteristic apoptotic fragment. These data indicate that through the coordinated regulation of membrane, mitochondrial and signaling events, B18L executes cancer cell death and thus has the potential to be developed into a potent and selective anti-cancer compound.

Targeting the ubiquitin-proteasome pathway to overcome anti-cancer drug resistance

2020 ◽  
Vol 48 ◽  
pp. 100663 ◽  
Author(s):  
Silpa Narayanan ◽  
Chao-Yun Cai ◽  
Yehuda G. Assaraf ◽  
Hui-Qin Guo ◽  
Qingbin Cui ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Drug ◽  
Ubiquitin Proteasome Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals Mechanisms of tRNA-derived fragments and tRNA halves in cancer treatment resistance

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Yue Zhang ◽  
Huizhu Qian ◽  
Jing He ◽  
Wen Gao
Keyword(s):  
Cancer Treatment ◽  
Cancer Progression ◽  
Treatment Resistance ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
New Ideas ◽  
Proliferation And Metastasis ◽  
Trna Halves ◽  
Cell Proliferation And Metastasis

Abstract The tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) are newly discovered noncoding RNAs in recent years. They are derived from specific cleavage of mature and pre-tRNAs and expressed in various cancers. They enhance cell proliferation and metastasis or inhibit cancer progression. Many studies have investigated their roles in the diagnosis, progression, metastasis, and prognosis of various cancers, but the mechanisms through which they are involved in resistance to cancer treatment are unclear. This review outlines the classification of tRFs and tiRNAs and their mechanisms in cancer drug resistance, thus providing new ideas for cancer treatment.

scholarly journals A Compendium of Information on the Lysosome

2021 ◽  
Vol 9 ◽  
Author(s):  
Nadia Bouhamdani ◽  
Dominique Comeau ◽  
Sandra Turcotte
Keyword(s):  
Drug Resistance ◽  
Scientific Knowledge ◽  
Targeted Therapies ◽  
Cancer Drug ◽  
Functional Changes ◽  
The Past ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Long Time ◽  
Signaling Organelles

For a long time, lysosomes were considered as mere waste bags for cellular constituents. Thankfully, studies carried out in the past 15 years were brimming with elegant and crucial breakthroughs in lysosome research, uncovering their complex roles as nutrient sensors and characterizing them as crucial multifaceted signaling organelles. This review presents the scientific knowledge on lysosome physiology and functions, starting with their discovery and reviewing up to date ground-breaking discoveries highlighting their heterogeneous functions as well as pending questions that remain to be answered. We also review the roles of lysosomes in anti-cancer drug resistance and how they undergo a series of molecular and functional changes during malignant transformation which lead to tumor aggression, angiogenesis, and metastases. Finally, we discuss the strategy of targeting lysosomes in cancer which could lead to the development of new and effective targeted therapies.

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