• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.104-114
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• 2024

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

• Korean Journal of Medicinal Crop Science
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• v.26 no.2
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• pp.141-147
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• 2018

Background: Astilbe chinensis (Maxim.) Franch. Et Savat. is a plant belonging to Saxifragaceae family and contains various active ingredients including astilbin and bergenin. It has been used as a traditional Korean medicine to improve fever, pain, and cough. Recently, a number of Korean medical resources have been studied for cancer and inflammation treatment, but A. chinensis (Maxim.) Franch. Et Savat. has not yet been investigated. Consequently, this study investigated the inhibitory effect of ethanol extracts from A. chinensis (Maxim.) Franch. Et Savat. (ARE) on oxidative stress and colorectal cancer using RAW264.7 and the human colorectal cancer cell line HCT-116. Methods and Results: In total, $500{\mu}g/m{\ell}$ ARE reduced cell viability by $38.96{\pm}1.32%$, and increased caspase-3 activity by $133.08{\pm}3.41%$ in HCT-116 cells. Moreover, TUNEL signaling and the early apoptosis ratio ($34.56{\pm}1.67%$) increased by $500{\mu}g/m{\ell}$ ARE treatment. $H_2O_2$-induced oxidative stress and cell death were diminished by $500{\mu}g/m{\ell}$ ARE treatment through decreasing ROS (reactive oxygen species). Conclusions: The inhibitory effects of ARE against human colorectal cancer cells is mediated by apoptosis and caspase-3 activation, and $H_2O_2$-induced ROS generation and cell death are decreased by ARE treatment in RAW264.7 cells. However, further study is required to explore how ARE treatment is involved in the signaling pathway to decrease ROS.

• BMB Reports
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• v.53 no.2
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• pp.88-93
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• 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.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.125-131
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• 2014

BACKGROUND/OBJECTIVES: The objective of this study was to evaluate the protective effect of black rice extract (BRE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. MATERIALS/METHODS: Methanolic extract from black rice was evaluated for the protective effect on TBHP-induced oxidative injury in HepG2 cells. Several biomarkers that modulate cell survival and death including reactive oxygen species (ROS), caspase-3 activity, and related cellular kinases were determined. RESULTS: TBHP induced cell death and apoptosis by a rapid increase in ROS generation and caspase-3 activity. Moreover, TBHP-induced oxidative stress resulted in a transient ERK1/2 activation and a sustained increase of JNK1/2 activation. While, BRE pretreatment protects the cells against oxidative stress by reducing cell death, caspase-3 activity, and ROS generation and also by preventing ERKs deactivation and the prolonged JNKs activation. Moreover, pretreatment of BRE increased the activation of ERKs and Akt which are pro-survival signal proteins. However, this effect was blunted in the presence of ERKs and Akt inhibitors. CONCLUSIONS: These results suggest that activation of ERKs and Akt pathway might be involved in the cytoprotective effect of BRE against oxidative stress. Our findings provide new insights into the cytoprotective effects and its possible mechanism of black rice against oxidative stress.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.526-537
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• 2023

Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.

• Anatomy and Cell Biology
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• v.57 no.1
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• pp.70-84
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• 2024

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.172-180
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• 2002

Polychlorinated biphenyls(PCBs) are large scale industrial chemicals which are using in diverse applications. The goal of this study was to determine if exposure to 2,2',5,5'-tetrachlorobiphenyl (PCB 52) leads to an increase in the production of active oxidants, and subsequently promotes apoptosis of neuronal SK-N-MC cells. Reactive oxygen species (ROS) formation was examined in SK-N-MC cells after treatment of PCB 52 by concentrations and incubation times, respectively. It showed that the rate of ROS production in the cells was increased in a does-dependent manner to 45 min, followed by a return towards control levels after 120 min treatment. We also examined the association of PCB-induced apoptosis with the modulation of biomakers of oxidative damage to lipids (malondialdehyde [MDA]) in SK-N-MC cells. Increased MDA was observed in a dose-dependent manner in groups treated with 10, 15, and 20 figJ me of PCB 52 for 24 h. After treatment of PCB 52, the cells did not show any significant change in the rate of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) activity. Whereas, the cells had a two-fold greater rate of change in catalase activity at 20 ㎍/㎖ of PCB 52 for 24 h when compared to control group. Korean Ginseng is one of the most important crude drugs which has been used as a traditional Oriental medicine. We next investigated protective effect of extracts of ginseng on cytotoxicity induced by PCB 52 in SK-N-MC cells. Pretreatment of SK-N-MC cells with 25-200 μg/ml of ginseng were reduced cell death in a dose-dependent manner in PCB 52-treated cells. To examine the sensitivity of beta-catenin to ginseng, the protective effect of a range of ginseng concentrations was examined in SK-N-MC cells treated with PCB 52. The result demonstrated that ginseng efficiently blocked PCB 52 inducible beta-catenin proteolysis in a concentration dependent manner. The ROS formation was also measured in the presences of extract of ginseng and superoxide dismutase (inhibitor of oxygen free radical production). The both SOD (400 U/ml) and ginseng (200 μg/ml) significantly inhibited RDS generation in PCB 52-treated group.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.499-507
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• 2024

Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether 1,3,5-trihydroxybenzene (THB), a compound abundant in marine products, might inhibit UVB radiationinduced NADPH oxidase 4 (NOX4) in both human HaCaT keratinocytes and mouse dorsal skin and explore its cytoprotective mechanism. The mechanism of action was determined using western blotting, immunocytochemistry, NADP⁺/NADPH assay, reactive oxygen species (ROS) detection, and cell viability assay. THB attenuated UVB-induced NOX4 expression both in vitro and in vivo, and suppressed UVB-induced ROS generation via NADP⁺ production, resulting in increased cell viability with decreased apoptosis. THB also reduced the expression of UVB-induced phosphorylated AMP-activated protein kinase (AMPK) and phosphorylated c-Jun N-terminal kinase (JNK). THB suppressed UVB-induced NOX4 expression and ROS generation by inhibiting AMPK and JNK signaling pathways, thereby inhibiting cellular damage. These results showed that THB could be developed as a UV protectant.

• Food Science and Biotechnology
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• v.17 no.5
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• pp.983-989
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• 2008

Two flavonoids, isorhamnetin 3-O-$\beta$-D-glucopyranoside (1) and quercetin 3-O-$\beta$-D-glucopyranoside (2), from slander glasswort (Salicornia herbacea, Korean name hamcho) were isolated. Antioxidative and matrix metalloproteinase-9(MMP-9) inhibitory effects of these compounds were investigated in HT 1080 cell lines. These compounds suppressed the electron spin resonance (ESR) signal intensity on generation of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical in a free-cellular system. Their scavenging effects on generation of intercellular reactive oxygen species (ROS) also exhibited similar trends with DPPH radical in the free cellular system. Also, a control group combined only with Fe(II)-$H_{2}O_2$ resulted in DNA apoptosis by oxidative stress, whereas treatments with these compounds suppressed radical-mediated DNA damage. Intracellular glutathione (GSH) levels were slightly increased in the presence of compound 1 and 2. Moreover, these compounds led to the reduction of the expression levels of MMP-9 without cytotoxic influence. These results suggest that these compounds have a potential as a valuable natural antioxidant and MMP inhibitor related to oxidative stress. Therefore, these compounds not only can be developed as a candidate for a therapeutic potential but also a source for use as ingredients of health foods or functional foods to prevent metastasis involving MMP-9, closely related to ROS.

• ALGAE
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• v.35 no.2
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• pp.189-200
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• 2020

Pyropia yezoensis has been used as functional food in East Asia, especially in Korea and Japan, for more than five hundred years. This study aims to evaluate the antioxidant effect of polyphenols and proteins-rich extracts from P. yezoensis (PPPs) against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative cell damage. Among six Korean local strains obtained from Jinhae (JiH), Haenam (HN), Jangheung (JaH), Jindo (JD), Wando (WD), and Sinan (SA) areas, the extracts of P. yezoensis from SA and JD are relatively higher in polyphenols and proteins contents. SA showed the lowest IC₅₀ scavenging activities against 1,1-diphenyl-2-picryl-hydrazyl and alkyl radicals and displayed protective effects against reactive oxygen species (ROS) in AAPH-induced Vero cells. Especially, the PPPs extracts from SA and JD showed protective activities against AAPH-induced apoptosis, as observed by nuclear staining with Hoechst 33342. Furthermore, in vivo studies of the SA extract in zebrafish showed significantly reduced ROS generation, lipid peroxidation, and cell damage. This is the first study, to our knowledge, to evaluate the antioxidant bioactivity of PPP in the Korean Peninsula using a zebrafish model. Due to SA and JD both located in the west coast of Korea, we deduced that the chemical content of the different PPP extracts was mildly influenced by their geographic location, and this alga has potential of protective activity against AAPH-induced ROS both in vitro and in vivo.