• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.93-100
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• 2014

Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like $H_2DCFDA$, JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5895-5900
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• 2013

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.

• Journal of Microbiology and Biotechnology
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• v.18 no.12
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• pp.1997-2003
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• 2008

Cordyceps militaris is well known as a traditional medicinal mushroom and has been shown to exhibit immunostimulatory and anticancer activities. In this study, we investigated the apoptosis induced by an aqueous extract of C. militaris (AECM) via the activation of caspases and altered mitochondrial membrane permeability in human breast cancer MDA-MB-231 cells. Exposure to AECM induced apoptosis, as demonstrated by a quantitative analysis of nuclear morphological change and a flow cytometric analysis. AECM increased hyperpolarization of mitochondrial membrane potential and promoted the activation of caspases. Both the cytotoxic effect and apoptotic characteristics induced by AECM treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. AECM-induced apoptosis was associated with the inhibition of Akt activation in a time-dependent manner, and pretreatment with LY294002, a PI3K/Akt inhibitor, significantly increased AECM-induced apoptosis. The results indicated that AECM-induced apoptosis may relate to the activation of caspase-3 and mitochondria dysfunctions that correlate with the inactivation of Akt.

• Korean Journal of Pharmacognosy
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• v.52 no.3
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• pp.149-156
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• 2021

Excessive glutamate can cause oxidative stress in neuronal cells and this can be the reason for neurodegenerative disease. In this study, we investigated the protective effect of Spirulina maxima hot ethanol extract on mouse hippocampal HT22 cell of which glutamate receptor has no function. HT22 cells were pre-treated with S. maxima sample at a dose dependent manner (1, 10 and 100 ㎍/ml). After an hour, glutamate was treated. Cell viability, reactive oxygen species (ROS) accumulation, Ca²⁺ influx, decrease of mitochondrial membrane potential level and glutathione related assays were followed by then. S. maxima ethanol extract improved the cell viability by suppressing the ROS and Ca²⁺ formation, retaining the mitochondrial membrane potential level and protecting the activity of the antioxidant enzymes compared with group of vehicle-treated controls. These suggest that S. maxima may decelerate the neurodegeneration by attenuating neuronal damage and oxidative stress.

• Herbal Formula Science
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• v.30 no.2
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• pp.59-66
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• 2022

Objectives : This study is to investigate whether Carthami flos exhibits a synergistic effect on the apoptotic effect of doxorubicin on human gastric cancer cells. Methods : We used AGS, a human gastric cancer cell line. To investigate the apoptotic efficacy of doxorubicin and Carthami flos, MTT and CCK-8 methods were used. To confirm apoptosis, cell cycle and mitochondrial membrane potential changes were confirmed. To investigate the mechanism of apoptosis, the reactive oxygen species (ROS) experiment was performed. Results : 1. Doxorubicin or Carthami flos induced cell death in the human gastric cancer cell line AGS. 2. Carthami flos showed a synergistic effect of cell death by doxorubicin. 3. The cell cycle and mitochondrial membrane potential changes revealed that cell death was apoptosis. 4. Apoptosis was related to reactive oxygen species (ROS) generation. Conclusions : This result shows the anticancer synergistic effect of Carthami flos in gastric cancer cells, and is considered to be an important basis for the development of anticancer drugs for Carthami flos.

• Natural Product Sciences
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• v.29 no.2
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• pp.67-73
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• 2023

Oxidative stress brings about apoptosis through various mechanisms. In particular, oxidative stress in neuronal cells can causes a variety of brain diseases. This study was conducted to investigate the effect of Bidens tripartita on oxidative stress in neuronal cells. B. tripartita has traditionally been used in Russia as a medicine for diseases such as rhinitis, angina and colitis. Over-production of glutamate induces oxidative stress. When the oxidative stress occurs in the cells, reactive oxygen species (ROS) and Ca²⁺ increase. In addition, the abrupt decline of mitochondrial membrane potential and the decrease of glutathione related enzymes such as glutathione reductase (GR) and glutathione peroxidase (GPx) are also observed. The samples used in the experiment showed cytoprotective effect in the MTT assay. It also lowered the ROS and Ca²⁺ level, and increased degree of mitochondrial membrane potential, GR and GPx. As a result, B. tripartita had a positive effect against oxidative stress. Thus, it is expected to have potential for treatment and prevention of degenerative brain diseases such as Alzheimer's disease.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.11
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• pp.1552-1556
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• 2005

The UCPs are members of the mitochondrial inner membrane transporter family, present in the mitochondrial inner membrane. Their main function is increasing the energy expenditure via diminishing the resulting production of ATP from mitochondrial oxidative phosphorylation instead of yielding dissipative heat. They are associated with the metabolism of fat and regulation of energy expenditure. The UCP gene can be viewed as the candidate gene for chicken fatness. In the present study, RT-PCR and Northern Blot methods were developed to investigate the expression of the UCP gene in ten tissues including heart, liver, spleen, lung, kidney, gizzard, intestine, brain, breast muscle and abdominal fat of chicken. The results of both RT-PCR and Northern Blot methods showed that the UCP gene expressed specific in breast muscle. The expression levels of UCP gene in breast muscles from egg-type and meat-type chickens of hatching, 2, 4, 6 and 8 wk of age were detected by RT-PCR assay and results showed that the expression levels of UCP gene were related to breeds. Expression level of UCP gene in layers was higher than that in broilers at various weeks of age except at 6 wk. The UCP gene's expression was higher at 6 wk and had no significant difference among other weeks of age in broilers; in layers the expression level of UCP gene had no significant difference among weeks of age. The experiment results also showed that insulin could increase the expression level of UCP gene by 40% compared with control group.

• Toxicological Research
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• v.35 no.1
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• pp.83-91
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• 2019

Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ${\geq}15{\mu}g/mL$, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures.

• BMB Reports
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• v.52 no.9
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• pp.566-571
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• 2019

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid ${\beta}$-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1876-1884
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• 2020

Ethanol often accumulates during the process of wine fermentation, and mitophagy has critical role in ethanol output. However, the relationship between mitophagy and ethanol stress is still unclear. In this study, the expression of ATG11 and ATG32 genes exposed to ethanol stress was accessed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The result indicated that ethanol stress induced expression of the ATG11 and ATG32 genes. The colony sizes and the alcohol yield of atg11 and atg32 were also smaller and lower than those of wild type strain under ethanol whereas the mortality of mutants is higher. Furthermore, compared with wild type, the membrane integrity and the mitochondrial membrane potential of atg11 and atg32 exhibited greater damage following ethanol stress. In addition, a greater proportion of mutant cells were arrested at the G1/G0 cell cycle. There was more aggregation of peroxide hydrogen (H2O2) and superoxide anion (O2•-) in mutants. These changes in H2O2 and O2•- in yeasts were altered by reductants or inhibitors of scavenging enzyme by means of regulating the expression of ATG11 and ATG32 genes. Inhibitors of the mitochondrial electron transport chain (mtETC) also increased production of H2O2 and O2•- by enhancing expression of the ATG11 and ATG32 genes. Further results showed that activator or inhibitor of autophagy also activated or inhibited mitophagy by altering production of H2O2 and O2•. Therefore, ethanol stress induces mitophagy which improves yeast the tolerance to ethanol and the level of mitophagy during ethanol stress is regulated by ROS derived from mtETC.