scholarly journals Oxyresveratrol Possesses DNA Damaging Activity

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2577
Author(s):  
Sarayut Radapong ◽  
Satyajit D. Sarker ◽  
Kenneth J. Ritchie

Artocarpus lakoocha Wall. ex Roxb. (family: Moraceae) has been used as a traditional Thai medicine for the treatment of various parasitic diseases. This species has been reported to be the source of phytochemicals, which show potent biological activities. The objective of this study was to investigate the phytochemical profile of the extracts of the heartwood of A. lakoocha and their pro-oxidant activity in vitro. The heartwood was ground, extracted, and then chromatographic and spectroscopic analyses were carried out; oxyresveratrol was identified as the major component in the extracts. The pro-oxidant activity was investigated using DNA-nick, reactive oxygen species and reducing assays. The results showed that oxyresveratrol induced DNA damage dose-dependently in the presence of copper (II) ions. It was also found to generate reactive oxygen species (ROS) in a dose-dependent manner and reduce copper (II) to copper (I). It is concluded that oxyresveratrol is the most abundant stilbenoid in A. lakoocha heartwood. The compound exhibited pro-oxidant activity in the presence of copper (II) ions, which may be associated with its ability to act as an anticancer compound.

2018 ◽  
Vol 64 (7) ◽  
pp. 455-464 ◽  
Author(s):  
Géssika Silva Souza ◽  
Lais Pessanha de Carvalho ◽  
Edésio José Tenório de Melo ◽  
Valdirene Moreira Gomes ◽  
André de Oliveira Carvalho

Plant defensins are plant antimicrobial peptides that present diverse biological activities in vitro, including the elimination of Leishmania amazonensis. Plant defensins are considered promising candidates for the development of new drugs. This protozoan genus has great epidemiological importance and the mechanism behind the protozoan death by defensins is unknown, thus, we chose L. amazonensis for this study. The aim of the work was to analyze the possible toxic mechanisms of Vu-Defr against L. amazonensis. For analyses, the antimicrobial assay was repeated as previously described, and after 24 h, an aliquot of the culture was tested for viability, membrane perturbation, mitochondrial membrane potential, reactive oxygen species (ROS) and nitric oxide (NO) inductions. The results of these analyses indicated that after interaction with L. amazonensis, the Vu-Defr causes elimination of promastigotes from culture, membrane perturbation, mitochondrial membrane collapse, and ROS induction. Our analysis demonstrated that NO is not produced after Vu-Defr and L. amazonensis interaction. In conclusion, our work strives to help to fill the gap relating to effects caused by plant defensins on protozoan and thus better understand the mechanism of action of this peptide against L. amazonensis.


Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770163 ◽  
Author(s):  
Niharika Sinha ◽  
Prashanta Kumar Panda ◽  
Prajna Paramita Naik ◽  
Tapas K Maiti ◽  
Sujit K Bhutia

The accumulating evidences show that Abrus agglutinin, a plant lectin, displays a broad range of anticancer activity including cancer-specific induction of apoptosis; however, the underlying molecular mechanism of Abrus agglutinin–induced oral cancer stem cell elimination remains elusive. Our data documented that Abrus agglutinin effectively downregulated the CD44+ expression with the increased CD44− population in different oral cancer cells. After 24-h Abrus agglutinin treatment, FaDu cells were quantified for orosphere formation in ultra-low attachment plates and data showed that Abrus agglutinin inhibited the number and size of orosphere in a dose-dependent manner in FaDu cells. Furthermore, Abrus agglutinin hindered the plasticity of FaDu orospheres as supported by reduced sphere formation and downregulated the self-renewal property via inhibition of Wnt-β-catenin signaling pathway. Introduction of LiCl, a glycogen synthase kinase 3β inhibitor, rescued the Abrus agglutinin–stimulated inhibition of β-catenin and phosphorylated glycogen synthase kinase 3β in FaDu cell–derived orospheres confirming importance of Wnt signaling in Abrus agglutinin–mediated inhibition of stemness. In this connection, our data showed that Abrus agglutinin restrained proliferation and induced apoptosis in FaDu-derived cancer stem cells in dose-dependent manner. Moreover, western blot data demonstrated that Abrus agglutinin increased the Bax/Bcl-2 ratio with activation of poly(adenosine diphosphate–ribose) polymerase and caspase-3 favoring apoptosis induction in orospheres. Abrus agglutinin induced reactive oxygen species accumulation in orospheres and pretreatment of N-acetyl cysteine, and a reactive oxygen species scavenger inhibited Abrus agglutinin–mediated caspase-3 activity and β-catenin expression indicating reactive oxygen species as a principal regulator of Wnt signaling and apoptosis. In conclusion, Abrus agglutinin has a potential role as an integrative therapeutic approach for combating oral cancer through targeting self-renewability of orospheres via reactive oxygen species–mediated apoptosis.


Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 316 ◽  
Author(s):  
Wanchun Su ◽  
Lei Wang ◽  
Xiaoting Fu ◽  
Liying Ni ◽  
Delin Duan ◽  
...  

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry.


2002 ◽  
Vol 46 (10) ◽  
pp. 3113-3117 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Kei Kondo ◽  
Nobuyuki Uehara ◽  
Seiko Otokozawa ◽  
Naoki Tsuji ◽  
...  

ABSTRACT We investigated the significance of endogenous reactive oxygen species (ROS) produced by fungi treated with miconazole. ROS production in Candida albicans was measured by a real-time fluorogenic assay. The level of ROS production was increased by miconazole at the MIC (0.125 μg/ml) and was enhanced further in a dose-dependent manner, with a fourfold increase detected when miconazole was used at 12.5 μg/ml. This increase in the level of ROS production was completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10 μM. In a colony formation assay, the decrease in cell viability associated with miconazole treatment was significantly prevented by addition of PDTC. Moreover, the level of ROS production by 10 clinical isolates of Candida species was inversely correlated with the miconazole MIC (r = −0.8818; P < 0.01). These results indicate that ROS production is important to the antifungal activity of miconazole.


2011 ◽  
Vol 23 (4) ◽  
pp. 561 ◽  
Author(s):  
Nathan T. Bain ◽  
Pavneesh Madan ◽  
Dean H. Betts

In vitro embryo production (IVP) suffers from excessive developmental failure. Its inefficiency is linked, in part, to reactive oxygen species (ROS) brought on by high ex vivo oxygen (O2) tensions. To further delineate the effects of ROS on IVP, the intracellular ROS levels of early bovine embryos were modulated by: (1) varying O2 tension; (2) exogenous H2O2 treatment; and (3) antioxidant supplementation. Although O2 tension did not significantly affect blastocyst frequencies (P > 0.05), 20% O2 accelerated the rate of first cleavage division and significantly decreased and increased the proportion of permanently arrested 2- to 4-cell embryos and apoptotic 9- to 16-cell embryos, respectively, compared with embryos cultured in 5% O2 tension. Treatment with H2O2, when applied separately to oocytes, zygotes, 2- to 4-cell embryos or 9- to 16-cell embryos, resulted in a significant (P < 0.05) dose-dependent decrease in blastocyst development in conjunction with a corresponding increase in the induction of either permanent embryo arrest or apoptosis in a stage-dependent manner. Polyethylene glycol–catalase supplementation reduced ROS-induced embryo arrest and/or death, resulting in a significant (P < 0.05) increase in blastocyst frequencies under high O2 culture conditions. Together, these results indicate that intracellular ROS may be signalling molecules that, outside an optimal range, result in various developmentally regulated modes of embryo demise.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Ping Hu ◽  
Yin-Bo Peng ◽  
Yi-Fan Zhang ◽  
Ying Wang ◽  
Wei-Rong Yu ◽  
...  

Reactive oxygen species (ROS) generated after tissue injury play a crucial role during wound healing through initiating acute inflammation, clarifying infection and dead tissue, and mediating various intracellular signal transduction. Prostaglandin E2 (PGE2) has been identified as one of the major factors responsible for inflammation and tissue repair. In this study, we tested our hypothesis that ROS produced by damaged human keratinocytes induces the synthesis of PGE2. In vitro epithelial wounding model was used to observe the production of ROS and secretion of PGE2 as well as the involved signal pathway. The mechanical injury caused the rapid production of ROS in in vitro cultured keratinocytes, which was significantly blocked by an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. The increased intracellular ROS caused by mechanical injury stimulates PGE2 production in a time-dependent manner via the activation of cyclooxygenase-2 (COX-2), which was stimulated by phosphorylation of extracellular signal-regulated protein kinase (ERK). These results indicate ROS-induced ERK activation leading to the activation of COX-2 and the synthesis of PGE2 in human keratinocytes responding to mechanical injury in the acute phase.


2001 ◽  
Vol 31 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Tobias W. Fischer ◽  
Georg Scholz ◽  
Brunhilde Knöll ◽  
Uta-Christina Hipler ◽  
Peter Elsner

2007 ◽  
Vol 85 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Xu-Bin Jing ◽  
Xian-Bin Cai ◽  
Hui Hu ◽  
Su-Zuan Chen ◽  
Bin-Ming Chen ◽  
...  

cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Δψm), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Δψm; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Δψm are events involved in the apoptotic pathway of EC-109 induced by CDDP.


2012 ◽  
Vol 12 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Claudia Jiménez-López ◽  
John R. Collette ◽  
Kimberly M. Brothers ◽  
Kelly M. Shepardson ◽  
Robert A. Cramer ◽  
...  

ABSTRACTThe interaction ofCandida albicanswith phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvationin vitroand is driven not by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species (ROS). Curiously, these genes are induced in a narrow window of sublethal ROS concentrations.C. albicanscells phagocytosed by primary macrophages deficient in thegp91phoxsubunit of the phagocyte oxidase do not express theARGpathway, indicating that the induction is dependent on the phagocyte oxidative burst.C. albicans argpathway mutants are retarded in germ tube and hypha formation within macrophages but are not notably more sensitive to ROS. We also find that theARGpathway is regulated not by the general amino acid control response but by transcriptional regulators similar to theSaccharomyces cerevisiaeArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner.


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