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NAC AND Mitochondria

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https://www.readbyqxmd.com/read/29289511/opening-of-voltage-dependent-anion-channels-promotes-reactive-oxygen-species-generation-mitochondrial-dysfunction-and-cell-death-in-cancer-cells
#1
David N DeHart, Diana Fang, Kareem Heslop, Li Li, John J Lemasters, Eduardo N Maldonado
Enhancement of aerobic glycolysis and suppression of mitochondrial metabolism characterize the pro-proliferative Warburg phenotype of cancer cells. High free tubulin in cancer cells closes voltage dependent anion channels (VDAC) to decrease mitochondrial membrane potential (ΔΨ), an effect antagonized by erastin, the canonical promotor of ferroptosis. Previously, we identified six compounds (X1-X6) that also block tubulin-dependent mitochondrial depolarization. Here, we hypothesized that VDAC opening after erastin and X1-X6 increases mitochondrial metabolism and reactive oxygen species (ROS) formation, leading to ROS-dependent mitochondrial dysfunction, bioenergetic failure and cell death...
December 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29229420/ros-mediated-oligomerization-of-vdac2-is-associated-with-quinocetone-induced-apoptotic-cell-death
#2
Xiayun Yang, Shusheng Tang, Daowen Li, Bin Li, Xilong Xiao
Quinocetone (QCT) has been approved and widely used as an animal feed additive in China since 2003. However, investigations indicate that QCT shows potential toxicity both in vitro and in vivo. Although voltage dependent anion channel 1 (VDAC1) involved in regulating QCT-induced apoptotic cell death has been established, the role of voltage dependent anion channel 2 (VDAC2) in QCT-induced toxicity remains unclear. In this study, we showed that QCT-induced cell death was coupled to VDAC2 oligomerization. Moreover, VDAC inhibitor 4, 4'-diisothiocyano stilbene-2, 2'-disulfonic acid (DIDS) alleviated QCT-induced cell death and VDAC2 oligomerization...
December 8, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29222055/autophagy-plays-a-protective-role-in-mn-induced-toxicity-in-pc12-cells
#3
Qian Zhou, Xiaolong Fu, Xueting Wang, Qin Wu, Yuanfu Lu, Jingshan Shi, James E Klaunig, Shaoyu Zhou
Excessive environmental or occupational exposure to manganese (Mn) is associated with increased risk of neuron degenerative disorders. Oxidative stress and mitochondrial dysfunction are the main mechanisms of Mn mediated neurotoxicity. Selective removal of damaged mitochondria by autophagy has been proposed as a protective mechanism against neuronal toxicant-induced neurotoxicity. Whether autophagic flux plays a role in Mn-induced cytotoxicity remains to be fully elucidated. The present study was designed to investigate the effect of Mn exposure on autophagy, and how modulation of autophagic flux alters the sensitivities of cells to Mn-elicited cytotoxicity...
December 6, 2017: Toxicology
https://www.readbyqxmd.com/read/29214600/apoptosis-induction-by-alantolactone-in-breast-cancer-mda-mb-231-cells-through-reactive-oxygen-species-mediated-mitochondrion-dependent-pathway
#4
Li Cui, Weiquan Bu, Jie Song, Liang Feng, Tingting Xu, Dan Liu, Wenbo Ding, Jianhua Wang, Changyang Li, Binge Ma, Yi Luo, Ziyu Jiang, Chengcheng Wang, Juan Chen, Jian Hou, Hongmei Yan, Lei Yang, Xiaobin Jia
Alantolactone is a sesquiterpene lactone isolated from Inula helenium L. Although alantolactone possesses anti-inflammation and apoptosis-induction activities, the underlying mechanism of anti-cancer effect on human breast cancer cells remains largely unknown. In this study, we explored the possibility of alantolactone as an apoptosis-inducing cytotoxic agent using MDA-MB-231 cells as in vitro model. Alantolactone significantly induced its apoptosis, demonstrated by cell cycle analysis, annexin V-APC/7-AAD double staining and dUTP nick end labeling...
December 6, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29157011/reactive-oxygen-species-modulate-itraconazole-induced-apoptosis-via-mitochondrial-disruption-in-candida-albicans
#5
Wonjong Lee, Dong Gun Lee
Itraconazole (ITC), a well-known fungistatic agent, has potent fungicidal activity against Candida albicans. However, its mechanism of fungicidal activity has not been elucidated yet, and we aimed to identify the mechanism of ITC against C. albicans. ITC caused cell shrinkage via potassium leakage though the ion channel. Since shrunken cells could indicate apoptosis, we investigated apoptotic features. Annexin V-FITC and TUNEL assays indicated that fungicidal activity of ITC was involved in apoptosis. Subsequently, we confirmed an intracellular factor that could cause apoptosis...
November 20, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29150332/organic-arsenicals-target-thioredoxin-reductase-followed-by-oxidative-stress-and-mitochondrial-dysfunction-resulting-in-apoptosis
#6
Xiao-Yang Fan, Yu-Jiao Liu, Kai Chen, Feng-Lei Jiang, Yan-Jun Hu, Dan Liu, Yi Liu, Yu-Shu Ge
Considering the vital role of cellular redox state, more and more researches focus on the design of drugs targeting thioredoxin reductase (TrxR), an important enzyme in maintaining the balance of cellular redox. Here two organic arsenicals, 2-(((4-(1,3,2-dithiarsinan-2-yl) phenyl) imino) methyl) phenol (PIM-PAO-PDT) and N-(4-(1,3,2-dithiarsinan-2-yl) phenyl)-2-hydroxybenzamide (PAM-PAO-PDT), bearing the S-As-S chemical scaffold and different linking groups have been synthesized, and both of them show the better inhibitory activity and selectivity towards HL-60 cells...
May 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29109043/individual-and-combined-effects-of-fusarium-toxins-on-apoptosis-in-pk15-cells-and-the-protective-role-of-n-acetylcysteine
#7
Wei Zhang, Shihua Zhang, Meiling Zhang, Lige Yang, Baojing Cheng, Jianping Li, Anshan Shan
Deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B1 (FB1) are among the most toxicologically important Fusarium toxins commonly found in nature that lead to nephrotoxicity in animals. The present study investigated that the individual and combined effects of subcytotoxic DON (0.25 μM), ZEN (20 μM) and FB1 (10 μM) on oxidative stress and apoptosis in porcine kidney cells (PK15). In addition, the protective effect of N-acetylcysteine (NAC) against the toxicity of Fusarium toxins was also evaluated...
November 7, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29100878/n-acetyl-l-cysteine-and-mn2-attenuate-cd2-induced-disturbance-of-the-intracellular-free-calcium-homeostasis-in-cultured-cerebellar-granule-neurons
#8
Nickolay K Isaev, Svetlana Avilkina, Sergey A Golyshev, Elisaveta E Genrikhs, Olga P Alexandrova, Marina R Kapkaeva, Elena V Stelmashook
Cadmium is a highly toxic heavy metal that is capable of accumulating in the body via direct exposure or through the alimentary and respiratory tract, leading to neurodegeneration. In this article, we show that the application of CdCl2 (0.001-0.005mM) for 48h induced high dose-dependent death rate of cultured cerebellar granule neurons (CGNs). Unlike Trolox or vitamin E, antioxidant N-acetyl-l-cysteine (NAC, 1mM) and Mn2+ (0.0025-0.005mM) significantly protected CGNs from this toxic effect. Using Fluo-4 AM, measurements of intracellular calcium ions demonstrated that 24h-exposure to Cd2+ induced intensive increase of Fluo-4 fluorescence in neurons accompanied by mitochondria swelling...
January 15, 2018: Toxicology
https://www.readbyqxmd.com/read/29064553/n-acetylcysteine-versus-progesterone-on-the-cisplatin-induced-peripheral-neurotoxicity
#9
Sherif Mohamed Zaki, Enas Mohamed Ahmed, Ahmed Galal Motawie, Sheeren Abdel Fattah
BACKGROUND AND AIMS: Cisplatin-induced peripheral nerve neurotoxicity (CIPN) is the main obstacle in cisplatin treatment. The aim of this study was to compare the modulatory effects of N-acetylcysteine (NAC) and progesterone on CIPN; up to knowledge, the protective effect of the progesterone on the CIPN is scarce in the literature. METHODS: 24 rats were divided into four groups: control, cisplatin-treated, concomitant cisplatin and NAC, and concomitant cisplatin and progesterone-treated...
October 24, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/28968984/a-novel-deubiquitinase-inhibitor-b-ap15-triggers-apoptosis-in-both-androgen-receptor-dependent-and-independent-prostate-cancers
#10
Jianyu Cai, Xiaohong Xia, Yuning Liao, Ningning Liu, Zhiqiang Guo, Jinghong Chen, Li Yang, Huidan Long, Qianqian Yang, Xiaolan Zhang, Lu Xiao, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Prostate cancer (PCa) remains a leading cause of cancer-related death in men. Especially, a subset of patients will eventually progress to the metastatic castrate-resistant prostate cancer (CRPC) which is currently incurable. Deubiquitinases (DUBs) associated with the 19S proteasome regulatory particle are increasingly emerging as significant therapeutic targets in numerous cancers. Recently, a novel small molecule b-AP15 is identified as an inhibitor of the USP14/UCHL5 (DUBs) of the 19S proteasome, resulting in cell growth inhibition and apoptosis in several human cancer cell lines...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28930188/cytotoxic-and-apoptotic-activities-of-prunus-spinosa-trigno-ecotype-extract-on-human-cancer-cells
#11
Stefania Meschini, Evelin Pellegrini, Maria Condello, Giovanni Occhionero, Sebastiano Delfine, Giancarlo Condello, Franco Mastrodonato
The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype (PsT) drupe extract with a nutraceutical activator complex (NAC) made of amino acids, vitamins and mineral salt blends, has shown in vitro anticancer activity. The cytotoxic effect of (PsT + NAC)(®) has been evaluated on human cancer cells, with an initial screening with colorectal, uterine cervical, and bronchoalveolar cells, and a subsequent focus on colon carcinoma cells HCT116 and SW480...
September 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28926928/curcumin-inhibited-growth-of-human-melanoma-a375-cells-via-inciting-oxidative-stress
#12
Wang Liao, Wei Xiang, Fei-Fei Wang, Rui Wang, Yan Ding
Curcumin, a polyphenol compound, possesses potent pharmacological properties in preventing cancers, which make it as a potential anti-cancer mediator. However, it is still unknown that whether Curcumin induced melanoma A375 cell was associated with oxidative stress. Here, we firstly found a fascinating result that Curcumin could reduce the proliferation and induced apoptosis of human melanoma A375 cells. Meanwhile, IC50 of Curcumin on A375 cells is 80μM at 48h. In addition, Curcumin caused oxidative stress through inducing further ROS burst, decreasing GSH, and wrecking mitochondria membrane potential (MMP), which were reversed by ROS inhibitor N-acetylcysteine (NAC)...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28901511/n%C3%A2-acetylcysteine-induces-apoptosis-via-the-mitochondria%C3%A2-dependent-pathway-but-not-via-endoplasmic-reticulum-stress-in-h9c2-cells
#13
Yuyong Liu, Ke Liu, Nian Wang, Huali Zhang
N‑acetylcysteine (NAC), a precursor of glutathione, is a widely used thiol‑containing antioxidant and modulator of the intracellular redox state. Our previous study demonstrated that excess reduced glutathione (GSH) from NAC treatment paradoxically led to a reduction in glutathione redox potential, increased mitochondrial oxidation and caused cytotoxicity at lower reactive oxygen species levels in H9c2 cells. However, no detailed data are available on the molecular mechanisms of NAC‑induced cytotoxicity on H9c2 cells...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28898446/contradictory-effects-of-mitochondria-and-non-mitochondria-targeted-antioxidants-on-hepatocarcinogenesis-by-altering-dna-repair
#14
Bibo Wang, Jing Fu, Ting Yu, An Xu, Wenhao Qin, Zhishi Yang, Yao Chen, Hongyang Wang
Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, it does not fully deny antioxidants for cancer prevention. Both tumor and antioxidants types influence the actual efficacy. However, little is known about the impact of different types of antioxidants on primary hepatocellular carcinoma (HCC), including non-mitochondrial- and mitochondrial-targeted antioxidants...
September 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28893509/non-thermal-plasma-induces-mitochondria-mediated-apoptotic-signaling-pathway-via-ros-generation-in-hela-cells
#15
Wei Li, K N Yu, Jie Ma, Jie Shen, Cheng Cheng, Fangjian Zhou, Zhiming Cai, Wei Han
Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. Although increasing evidence suggests that NTP selectively induces apoptosis in some types of tumor cells, the molecular mechanisms underlying this phenomenon remain unclear. In this study, we further investigated possible molecular mechanisms for NTP-induced apoptosis of HeLa cells. The results showed that NTP exposure significantly inhibited the growth and viability of HeLa cells. Morphological observation and flow cytometry analysis demonstrated that NTP exposure induced HeLa cell apoptosis...
November 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28842551/induction-of-mitochondrial-dysfunction-and-oxidative-damage-by-antibiotic-drug-doxycycline-enhances-the-responsiveness-of-glioblastoma-to-chemotherapy
#16
Qian Tan, Xiaoqiong Yan, Lin Song, Hongxiang Yi, Ping Li, Guobin Sun, Danfang Yu, Le Li, Zheng Zeng, Zhenlin Guo
BACKGROUND Inducing mitochondrial dysfunction has been recently demonstrated to be an alternative therapeutic strategy for cancer treatment. Doxycycline is an antibiotic that has been shown to have anti-cancer activities in various cancers by way of targeting mitochondria. In this work, we examined whether doxycycline can be repurposed for glioblastoma treatment. MATERIAL AND METHODS The effects of doxycycline on the growth, survival, and mitochondrial metabolisms of glioblastoma were investigated. The efficacy of a combination of doxycycline with temozolomide was examined using xenograft mouse model in total number of 40 mice...
August 26, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28831476/phenylarsine-oxide-pao-induces-apoptosis-in-hepg2-cells-via-ros-mediated-mitochondria-and-er-stress-dependent-signaling-pathways
#17
Ping Huang, Yu Hua Zhang, Xiao Wei Zheng, Yu Jia Liu, Hong Zhang, Luo Fang, Yi Wen Zhang, Chang Yang, Khairul Islam, Chao Wang, Hua Naranmandura
Arsenic trioxide (As2O3) is an old drug that has recently been reintroduced as a therapeutic agent for acute promyelocytic leukemia (APL). Although As2O3 is also applied to treat other types of cancer in vitro and in vivo, it has been reported that single agent As2O3 has poor efficacy against non-hematologic malignant cancers in clinical trials. Recently, a few reports have indicated that organic arsenic compounds can be a possible alternative for the treatment of As2O3-resistant cancers. In this study, we aimed to investigate whether the organic arsenic compound phenylarsine oxide (PAO) has potent cytotoxic effects against human hepatocellular carcinoma (HCC) HepG2 cells...
August 23, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28819639/antioxidant-treatment-in-male-mice-prevents-mitochondrial-and-synaptic-changes-in-an-nmda-receptor-dysfunction-model-of-schizophrenia
#18
Aarron Phensy, Christopher Driskill, Karen Lindquist, Lan Guo, Vivek Jeevakumar, Bryan Fowler, Heng Du, Sven Kroener
Glutamate theories of schizophrenia suggest that the disease is associated with a loss of NMDA receptors, specifically on GABAergic parvalbumin-expressing interneurons (PVIs), leading to changes in the excitation-inhibition balance in the prefrontal cortex (PFC). Oxidative stress contributes to the loss of PVI and the development of schizophrenia. Here, we investigated whether the glutathione precursor N-acetyl cysteine (NAC) can prevent changes in synaptic transmission at pyramidal cells and PVIs that result from developmental NMDAR blockade and how these changes are related to mitochondrial dysfunction in the PFCs of mice...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28795692/the-novel-resveratrol-derivative-3-5-diethoxy-3-4-dihydroxy-trans-stilbene-induces-mitochondrial-ros-mediated-er-stress-and-cell-death-in-human-hepatoma-cells-in-vitro
#19
Jae-Woo Park, Woo-Gyun Choi, Phil-Jun Lee, Su-Wol Chung, Byung-Sam Kim, Hun-Taeg Chung, Sungchan Cho, Jong-Heon Kim, Byoung-Heon Kang, Hyoungsu Kim, Hong-Pyo Kim, Sung-Hoon Back
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a well-known polyphenol that is present in grapes, peanuts, pine seeds, and several other plants. Resveratrol exerts deleterious effects on various types of human cancer cells. Here, we analyzed the cell death-inducing mechanisms of resveratrol-006 (Res-006), a novel resveratrol derivative in human liver cancer cells in vitro. Res-006 was more effectively suppressed the viability of HepG2 human hepatoma cells than resveratrol (the IC50 values were 67.2 and 354...
November 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28767417/a-novel-deubiquitinase-inhibitor-b-ap15-triggers-apoptosis-in-both-androgen-receptor-dependent-and-independent-prostate-cancers
#20
Jianyu Cai, Xiaohong Xia, Yuning Liao, Ningning Liu, Zhiqiang Guo, Jinghong Chen, Li Yang, Huidan Long, Qianqian Yang, Xiaolan Zhang, Lu Xiao, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Prostate cancer (PCa) remains a leading cause of cancer-related death in men. Especially, a subset of patients will eventually progress to the metastatic castrate-resistant prostate cancer (CRPC) which is currently incurable. Deubiquitinases (DUBs) associated with the 19S proteasome regulatory particle are increasingly emerging as significant therapeutic targets in numerous cancers. Recently, a novel small molecule b-AP15 is identified as an inhibitor of the USP14/UCHL5 (DUBs) of the 19S proteasome, resulting in cell growth inhibition and apoptosis in several human cancer cell lines...
June 28, 2017: Oncotarget
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