Water-soluble version of SCR7-pyrazine inhibits DNA repair and abrogates tumor cell proliferation Monica Pandey, Vidya Gopalakrishnan, Hassan A Swarup, Sujeet Kumar, Radha Gudapureddy, Anjana Elizabeth Jose, Supriya V Vartak, Robin Sebastian, Mrinal Srivastava, Bibha Choudhary, Mantelingu Kempegowda, Subhas S Karki, Sathees C Raghavan Journal of Radiation and Cancer Research 2019 10(1):27-43 Aim: Mammalian DNA Ligases play pivotal role in processes such as DNA replication, recombination, and repair, which qualifies them as potent therapeutic targets to eradicate cancer cells. Recently, we have identified a small molecule inhibitor, SCR7 and its oxidized form SCR7-pyrazine (2-mercapto-6,7-diphenylpteridin-4-ol) (SCR7-P), which can inhibit nonhomologous end-joining (NHEJ) in a Ligase IV-dependent manner. In the present study, we describe a water-soluble version of ligase inhibitor, sodium salt of SCR7-P (Na-SCR7-P) and its anti-tumor effects. Materials and Methods: Water soluble version of SCR7-P was synthesised. To study the inhibitory effect of Na-SCR7-P on ligases, we did in vitro DNA end joining assays using double strand DNA substrates. For this, different concentrations of Na-SCR7-P was used along with purified ligases or cell-free extracts. Further, cytotoxicity induced by Na-SCR7-P was evaluated through trypan blue exclusion assay, JC-1 assay and cell cycle analysis. Anti-tumor activity of Na-SCR7-P was investigated in Swiss albino mice and its off-target effects were studied by conducting kidney and liver test and histological evaluation. Further, the anti-angiogenic effect of the compound was studied using in ovo chorioallantoic membrane assay. Results: Na-SCR7-P inhibited NHEJ in a Ligase IV-dependent manner. However, unlike SCR7 and SCR7-P, it blocked joining catalyzed by all three ligases in vitro, making it an ideal cancer therapeutic agent, as it may target multiple DNA transaction processes within the cancer cells. Na-SCR7-P decreased mitochondrial membrane potential (MMP) leading to cell death in cancer cells. Importantly, the administration of Na-SCR7-P led to a significant reduction in tumor growth from 12th day of treatment, and its impact was significantly higher than previously described SCR7, which targets Ligase IV within cells. Antitumor activity of Na-SCR7-P in mice resulted in enhanced lifespan, with minimal side effects. In addition, the in ovo chorioallantoic membrane assay revealed potent antiangiogenic property of Na-SCR7-P. Conclusion: Our results suggest that Na-SCR7-P can target NHEJ and other DNA repair pathways by disrupting Ligase mediated joining and can potentially be used as a strategy for cancer treatment, owing to its water solubility. |
ΩτοΡινοΛαρυγγολόγος Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,
Translate
Ετικέτες
Τετάρτη 22 Μαΐου 2019
Αναρτήθηκε από
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
στις
10:47 μ.μ.
Ετικέτες
00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Αρχειοθήκη ιστολογίου
-
►
2023
(278)
- ► Φεβρουαρίου (139)
- ► Ιανουαρίου (139)
-
►
2022
(1962)
- ► Δεκεμβρίου (107)
- ► Σεπτεμβρίου (158)
- ► Φεβρουαρίου (165)
- ► Ιανουαρίου (163)
-
►
2021
(3614)
- ► Δεκεμβρίου (152)
- ► Σεπτεμβρίου (271)
- ► Φεβρουαρίου (64)
- ► Ιανουαρίου (357)
-
►
2020
(3279)
- ► Δεκεμβρίου (396)
- ► Σεπτεμβρίου (157)
- ► Φεβρουαρίου (382)
- ► Ιανουαρίου (84)
-
▼
2019
(11718)
- ► Δεκεμβρίου (265)
- ► Σεπτεμβρίου (545)
-
▼
Μαΐου
(1970)
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Pulmonary pleomorphic carcinoma harboring epide...
- Cervical cancer with breast metastasisChing-Tin...
- Inflammatory Pseudotumor of the LiverTsen-Long ...
- Pembrolizumab-induced uveitis in a patient with...
- Detection of anaplastic lymphoma kinase gene re...
- A Patient with refractory metastatic germ cell ...
- Modulation of oxidative stress by doxorubicin l...
- Antiproliferative effect of oxidative stress in...
- High-intensity focused ultrasound for localized...
- Prevention and management catheter-associated uri...
- people suffering from special phobiasAlireza Sang...
- singing on the happiness of older peopleMaryam En...
- Modeling of cardiac function of patients with a...
- patients with spinal muscular atrophy ,Ali-Asghar...
- Effect of cognitive behavior therapy integrated w...
- Warning System Designed to Predict Severe Sepsis ...
- Neurologic Complications of Infective Endocardi...
- Myeloid-Derived Suppressor Cells Mediate Immunosu...
- Tumour Spheroids-on-a-Chip ,M Ibrahim Khot, Mark ...
- Cancer Research and Practice
- Nursing and Midwifery Sciences
- Critical Care Medicine
- Podcast: Being a Professional Musician with Bipola...
- Medicine by Alexandros G. Sfakianakis,Anapafseos 5...
- Adjuvant therapies in venous leg ulcer management...
- Pressure Ulcer Summit 2018: An Interdisciplinary ...
- Leukemia inhibitory factor promotes the regenerat...
- Toll like receptors (TLRs) in response to human...
- Evaluation of hypercalciuria in patients receiv...
- Cytochemical tests to investigate sperm DNA dam...
- Family Medicine and Primary Care
- IL‐17A is not a treatment target in progressiv...
- The next‐generation BET inhibitor, PLX51107, d...
- Otolaryngology & Head and Neck Surgery
- Tropical Medicine
- Treating the primary in metastatic prostate cance...
- Cytoreductive nephrectomy in metastatic kidney ...
- Treating advanced penile cancer: where do we st...
- Supplemental oxygen for the management of dyspn...
- Multidimensional measurement of breathlessness:...
- Interdisciplinary management of chronic breath...
- Supportive and Palliative Care
- Organ Transplantation
- Serum carcinoembryonic antigen to predict recurre...
- Precision medicine in the ageing world: The role ...
- Prognostic roles of microRNA 143 and microRNA 145...
- Elevated neutrophil to lymphocyte and platelet to...
- Associated measurement of fucosylated levels of A...
- Clinicopathological and prognostic significance o...
- β-Arrestin-1 expression and epithelial-to-mesench...
- Prognostic nomogram for patients with non-metasta...
- Clinicopathological and molecular differences in ...
- Performance of a MethyLight assay for methylated ...
- Cell-free microRNAs as non-invasive biomarkers in...
- Urinary markers in treatment monitoring of lung c...
- Circular RNA ABCB10 promotes tumor progression an...
- Predictive significance of CYFRA21-1, squamous ce...
- Clinical significance of tumor miR-21, miR-221, m...
- The serum level of CC chemokine ligand 18 correla...
- iTRAQ-based proteomics reveals SOD2 as a potentia...
- New and old biomarkers in the differential diagno...
- Prognostic markers affecting the early recurrence...
- Cancer registries - guardians of breast cancer bi...
- Automated Pupillometry Devices in Critically Il...
- Language Monitoring in Brain Surgery Under Gene...
- Subanesthetic Dose of Ketamine Improved CFA-ind...
- Defining a Taxonomy of Intracranial Hypertensio...
- Pain Anxiety as a Mechanism Linking Pain Severi...
- The Association Between Antenatal Maternal Self...
- Prenatal Practice Staff Perceptions of Three Su...
- Exploring the Effects of Vitamin D Supplementat...
- How Might Maternal Poverty Impact the Course of...
- Poverty and Excess Length of Hospital Stay in Neo...
- The Effect of Depth of Anesthesia on Hemodynam...
- Neurosurgical Anesthesiology
- Addiction Medicine
- Vehicle Collision : Blunt rupture of the myocardiu...
- Variability in international normalized ratio a...
- Promotility Agents For The Treatment Of Ileus I...
- Ketamine Infusion for Pain Control in Adult Pat...
- Resuscitative Endovascular Balloon Occlusion of...
- Trauma and Acute Care Surgery
- Unfractionated heparin attenuates histone-mediat...
- Wall Contrast Enhancement of Thrombosed Intracran...
- Assessment of Explicitly Stated Interval Change o...
- Deep Learning–Based Automatic Segmentation of Lum...
- Hazardous Materials
- Sugar Alternatives : Molasses,Raw Honey,Stevia,Xyl...
- The Hearing Journal
- Molecular markers used to guide treatment, assess ...
- Programmed death-ligand 1 (PD-L1) also known as cl...
- Anaplastic lymphoma kinase (ALK) also known as ALK...
- Proto-oncogene tyrosine-protein kinase ROS is an e...
- The KRAS gene provides instructions for making a p...
- Amplification, also known as the over-expression o...
- Mutations that lead to EGFR overexpression (known ...
- A BRCA mutation is a mutation in either of the BRC...
- BRAF is a human gene that encodes a protein called...
- Differences in the Intended Meaning of Congest...
- ► Φεβρουαρίου (1143)
- ► Ιανουαρίου (744)
-
►
2017
(2)
- ► Φεβρουαρίου (1)
- ► Ιανουαρίου (1)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου