Antioxidant activity in sugarcane juice and its protective role against radiation induced DNA damage

2008 ◽  
Vol 106 (3) ◽  
pp. 1154-1160 ◽  
Author(s):  
U.S. Kadam ◽  
S.B. Ghosh ◽  
Strayo De ◽  
P. Suprasanna ◽  
T.P.A. Devasagayam ◽  
...  
Author(s):  
Rodrigo Gutierrez-Quintana ◽  
David J Walker ◽  
Kaye J Williams ◽  
Duncan M Forster ◽  
Anthony J Chalmers

Abstract Radiotherapy (RT) plays a fundamental role in the treatment of glioblastoma (GBM). GBM are notoriously invasive and harbour a subpopulation of cells with stem-like features which exhibit upregulation of the DNA damage response and are radioresistant. High radiation doses are therefore delivered to large brain volumes and are known to extend survival but also cause delayed toxicity with 50-90% of patients developing neurocognitive dysfunction. Emerging evidence identifies neuroinflammation as a critical mediator of the adverse effects of RT on cognitive function. In addition to its well-established role in promoting repair of radiation induced DNA damage, activation of poly(ADP-ribose) polymerase (PARP) can exacerbate neuroinflammation by promoting secretion of inflammatory mediators. Therefore, PARP represents an intriguing mechanistic link between radiation-induced activation of the DNA damage response and subsequent neuroinflammation. PARP inhibitors have emerged as promising new agents for GBM when given in combination with RT, with multiple preclinical studies demonstrating radiosensitizing effects and at least three compounds being evaluated in clinical trials. We propose that concomitant use of PARP inhibitors could reduce radiation-induced neuroinflammation and reduce the severity of radiation-induced cognitive dysfunction while at the same time improving tumour control by enhancing radiosensitivity.


Author(s):  
K. Soumya ◽  
Jesna James ◽  
T. M. Archana ◽  
A. T. Dhanya ◽  
A. P. Shahid ◽  
...  

Abstract Background DNA in a human cell is subjected to constant assault from both environmental factors and normal metabolic processes. Accumulation of DNA damage drives the progression of many health disorders like aging, cancer, diabetes, and neurodegenerative disorders. Results The present study focuses on the isolation of phenolic compound from the fruit of Terminalia chebula and its protective role on induced DNA damage. Diethyl ether and ethyl acetate extract of Terminalia chebula fruit were subjected to column chromatographic purification, and the fractions obtained were tested for the presence of phenolics. Fraction-12 isolated from diethyl ether extract was identified as gallic acid, which is used for cytotoxic and DNA damage protection activity assays. To select a non-toxic concentration of isolated compound, cytotoxicity was assessed by MTT assay. Gallic acid showed moderate toxicity at the highest concentration tested (i.e., percentage cell viability at 100 μg/ml is 40.51 ± 1.31). Antigenotoxic effect of gallic acid on HeLa cells was carried by alkaline comet assay. The compound showed significant protective abilities against hydrogen peroxide-induced DNA damage in HeLa cells. Conclusion These results show the importance of gallic acid isolated from Terminalia chebula fruit, as protector of oxidative stress-induced DNA damage.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiraporn Kantapan ◽  
Siwaphon Paksee ◽  
Aphidet Duangya ◽  
Padchanee Sangthong ◽  
Sittiruk Roytrakul ◽  
...  

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.


2002 ◽  
Vol 43 (2) ◽  
pp. 153-153 ◽  
Author(s):  
REMA RAJAGOPALAN ◽  
KHALIDA WANI ◽  
NAGARAJ G. HUILGOL ◽  
TSUTOMU V. KAGIYA ◽  
CHERUPALLY K. KRISHNAN NAIR

Oncogene ◽  
2006 ◽  
Vol 26 (16) ◽  
pp. 2365-2373 ◽  
Author(s):  
A M Ghaleb ◽  
J P Katz ◽  
K H Kaestner ◽  
J X Du ◽  
V W Yang

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3843
Author(s):  
Jeffrey R. Whiteaker ◽  
Tao Wang ◽  
Lei Zhao ◽  
Regine M. Schoenherr ◽  
Jacob J. Kennedy ◽  
...  

The ATM serine/threonine kinase (HGNC: ATM) is involved in initiation of repair of DNA double-stranded breaks, and ATM inhibitors are currently being tested as anti-cancer agents in clinical trials, where pharmacodynamic (PD) assays are crucial to help guide dose and scheduling and support mechanism of action studies. To identify and quantify PD biomarkers of ATM inhibition, we developed and analytically validated a 51-plex assay (DDR-2) quantifying protein expression and DNA damage-responsive phosphorylation. The median lower limit of quantification was 1.28 fmol, the linear range was over 3 orders of magnitude, the median inter-assay variability was 11% CV, and 86% of peptides were stable for storage prior to analysis. Use of the assay was demonstrated to quantify signaling following ionizing radiation-induced DNA damage in both immortalized lymphoblast cell lines and primary human peripheral blood mononuclear cells, identifying PD biomarkers for ATM inhibition to support preclinical and clinical studies.


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