• BMB Reports
• /
• 제53권2호
• /
• pp.88-93
• /
• 2020

Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatin-sensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROS-mediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.

• Biomolecules & Therapeutics
• /
• 제24권3호
• /
• pp.312-319
• /
• 2016

Human skin cells undergo pathophysiological processes via generation of reactive oxygen species (ROS) upon excessive exposure to ultraviolet B (UVB) radiation. This study investigated the ability of hesperidin ($C_{28}H_{34}O_{15}$) to prevent apoptosis due to oxidative stress generated through UVB-induced ROS. Hesperidin significantly scavenged ROS generated by UVB radiation, attenuated the oxidation of cellular macromolecules, established mitochondrial membrane polarization, and prevented the release of cytochrome c into the cytosol. Hesperidin downregulated expression of caspase-9, caspase-3, and Bcl-2-associated X protein, and upregulated expression of B-cell lymphoma 2. Hesperidin absorbed wavelengths of light within the UVB range. In summary, hesperidin shielded human keratinocytes from UVB radiation-induced damage and apoptosis via its antioxidant and UVB absorption properties.

• BMB Reports
• /
• 제34권1호
• /
• pp.43-46
• /
• 2001

$\alpha$-Phenyl-N-t-butylnitrone (PBN) is one of the most widely used spin-trapping compounds for investigating the existence of free radicals in biological systems. Recently, there has been considerable interest in the antioxidant nature of PBN on degenerative diseases, presumably related to oxidative stress. In the present study, the protective effect of PBN on the HepG2 cell line under oxidative stress was investigated. When the HepG2 cells were exposed to oxidant, such as hydrogen peroxide, menadione, or ethanol, the protective role of PBN was manifested as a reduction in trypan blue uptake and a decrease in the endogenous production of oxidants, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin. The modulation of activity of major antioxidant enzymes, such as superoxide dismutase and catalase, was not significantly different either in the presence or in the absence of PBN. This indicates that PBN acts as a direct scavenger of reactive oxygen species.

• Clinical and Experimental Pediatrics
• /
• 제56권3호
• /
• pp.107-111
• /
• 2013

Preterm infants are vulnerable to the oxidative stress due to the production of large amounts of free radicals, antioxidant system insufficiency, and immature oligodendroglial cells. Reactive oxygen species (ROS) play a pivotal role in the development of periventricular leukomalacia. The three most common ROS are superoxide ($O2^{\cdot-}$), hydroxyl radical ($OH^{\cdot}$), and hydrogen peroxide ($H_2O_2$). Under normal physiological conditions, a balance is maintained between the production of ROS and the capacity of the antioxidant enzyme system. However, if this balance breaks down, ROS can exert toxic effects. Superoxide dismutase, glutathione peroxidase, and catalase are considered the classical antioxidant enzymes. A recently discovered antioxidant enzyme family, peroxiredoxin (Prdx), is also an important scavenger of free radicals. Prdx1 expression is induced at birth, whereas Prdx2 is constitutively expressed, and Prdx6 expression is consistent with the classical antioxidant enzymes. Several antioxidant substances have been studied as potential therapeutic agents; however, further preclinical and clinical studies are required before allowing clinical application.

• 동의생리병리학회지
• /
• 제17권3호
• /
• pp.787-790
• /
• 2003

It has been demonstrated that oxidative stress of reactive oxygen species(ROS) may be a causative factor in the pathogenesis of bony disorder. The purpose of this study was to evaluate the oxidative stress of glucose oxidase(GO) in the cultured mouse osteoblasts and the protective effect of Alii Macrostemi Bulbus(AMB) on ROS-induced osteotoxicity. Toxic effect of GO and protective effect of AMB were carried out by colorimetric assay. 20mU/mi GO decreased cell viability dose-dependently, and AMB increased cell viability against GO-induced cytotoxicity in these cultures. From above the results. GO has toxic effect, and AMB is very effective on GO-induced osteotoxicity in cultured osteoblasts of neonatal mouse.

• Biomolecules & Therapeutics
• /
• 제24권6호
• /
• pp.616-622
• /
• 2016

Baicalein (5,6,7-trihydroxy-2-phenyl-chromen-4-one) is a flavone, a type of flavonoid, originally isolated from the roots of Scutellaria baicalensis. This study evaluated the protective effects of baicalein against oxidative damage-mediated apoptosis induced by ultraviolet B (UVB) radiation in a human keratinocyte cell line (HaCaT). Baicalein absorbed light within the wavelength range of UVB. In addition, baicalein decreased the level of intracellular reactive oxygen species (ROS) in response to UVB radiation. Baicalein protected cells against UVB radiation-induced DNA breaks, 8-isoprostane generation and protein modification in HaCaT cells. Furthermore, baicalein suppressed the apoptotic cell death by UVB radiation. These findings suggest that baicalein protected HaCaT cells against UVB radiation-induced cell damage and apoptosis by absorbing UVB radiation and scavenging ROS.

• BMB Reports
• /
• 제42권8호
• /
• pp.500-505
• /
• 2009

Anti-oxidative effect of Phellinus linteus (P. linteus) and red ginseng extracts on DNA damage induced by reactive oxygen species (ROS) were investigated in this study. P. linteus (PLE) and red ginseng extracts (RGE) inhibited the breaking of E. coli ColE1 plasmid DNA strands as well as nuclear DNA of rat hepatocytes damaged by oxidative stress. In addition, a reaction mixture of PLE and RGE showed synergistic inhibitory effect against DNA damage. These results suggest that PLE and RGE have a cellular defensive effect against DNA damage induced by ROS.

• Animal Bioscience
• /
• 제36권3호
• /
• pp.385-403
• /
• 2023

Male fertility is affected by multiple endogenous stressors, including reactive oxygen species (ROS), which greatly deteriorate the fertility. However, physiological levels of ROS are required by sperm for the proper accomplishment of different cellular functions including proliferation, maturation, capacitation, acrosomal reaction, and fertilization. Excessive ROS production creates an imbalance between ROS production and neutralization resulting in oxidative stress (OS). OS causes male infertility by impairing sperm functions including reduced motility, deoxyribonucleic acid damage, morphological defects, and enhanced apoptosis. Several in-vivo and in-vitro studies have reported improvement in quality-related parameters of sperm following the use of different natural and synthetic antioxidants. In this review, we focus on the causes of OS, ROS production sources, mechanisms responsible for sperm damage, and the role of antioxidants in preserving sperm fertility.

• Molecules and Cells
• /
• 제40권4호
• /
• pp.280-290
• /
• 2017

Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers ($eIF2{\alpha}$ phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases.

• 대한본초학회지
• /
• 제28권4호
• /
• pp.57-62
• /
• 2013

Objectives : Lonicerae Japonicae Flos (LJF) has been shown anti-oxidant, anti-inflammatory, anti-viral, anti-rheumatoid properties. However, it is still largely unknown whether LJF inhibits skin injury against oxidative stress in human keratinocyte, HaCaT cells. The purpose of this study was to evaluate the protective effects of LJF against hydrogen peroxide($H_2O_2$)-induced oxidative stress in human keratinocytes, HaCaT cells. Methods : To evaluate out the protective effects of LJF on oxidative injury in HaCaT cells, an oxidative stress model of HaCaT cells was established under a suitable concentration (500 ${\mu}M$) hydrogen peroxide. HaCaT keratinocyte cells were pre-treated with LJF (0.1, 0.25 or 0.5 mg/ml), and then stimulated with $H_2O_2$. Then, the cells were harvested to measure the cell viability, DNA damage, and release of reactive oxygen species (ROS). Results : LJF (0.1, 0.25 or 0.5 mg/ml) itself did not show any significant toxicity in HaCaT cells. The treatment of $H_2O_2$ caused the oxidative stress, leading to the cell death, and DNA injury. However, pretreatment with LJF reduced cell death, and DNA injury. The stimulation of $H_2O_2$ on HaCaT cells resulted in excessive release of ROS, which is the main factor of oxidative stress. The excessive release of ROS was inhibited by LJF treatment significantly. Conclusions : These results could suggest that LJF exhibited the protective effects of HaCaT cells against $H_2O_2$-induced oxidative stress by inhibiting ROS release. It could be explained that LJF inhibit skin damages against oxidative stress. Thus, LJF would be useful for the development of drug or cosmetics treating skin troubles.