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NAC AND Mitochondria

Ri-Zhen Huang, Xiao-Chao Huang, Bin Zhang, Hai-Yang Jia, Zhi-Xin Liao, Heng-Shan Wang
BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of cancer death, and novel chemotherapeutic drugs for treating HCC are urgently needed. 16-O-caffeoyl-16-hydroxylhexadecanoic acid (CHHA) is a new phenylpropanoid isolated by our group from Euphorbia nematocypha which is commonly used to treat solid tumors. However, the underlying mechanisms responsible for the CHHA-induced apoptosis in cancer cells, particularly in HCC, remain unknown. PURPOSE: In the present work, we evaluated the growth inhibitory effect of CHHA on HCC cells and explored the underlying molecular mechanisms...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Shuqiang Sun, Chunxiao Zhang, Jiahao Gao, Qiongyu Qin, Yaya Zhang, Hua Zhu, Xinjun Yang, Dongren Yang, Hongtao Yan
Benzene exposure affects the hematopoietic system and leads to the occurrence of various types of leukemia and hematotoxicity. It has been confirmed that active metabolites of benzene, including 1,4-benzoquinone (1,4-BQ), can induce reactive oxygen species (ROS) and apoptosis in the bone marrow, and recent studies have also suggested that benzene exposure can affect mitochondrial function in both experimental animals and cell lines. However, the potential relationship among ROS production, mitochondrial damages, and subsequent apoptosis following benzene exposure has not been well studied in detail...
January 1, 2018: Toxicology and Industrial Health
Xiaoting Jin, Bin Xue, Qunfang Zhou, Ruijun Su, Zhuoyu Li
Mitochondria can be used as important biomarkers of pollutants on human health, and fine particulate matter (PM2.5 ) has been documented to cause respiratory damage. However, current studies about the relationship between PM2.5 and mitochondria in respiratory tract are limited and warrant further detailed investigations. Hence, the study was aimed to evaluate effects of PM2.5 on mitochondrial structure, investigate the link between PM2.5 -induced mitochondrial disorder and respiratory damage, and delineate the possible mechanisms using both in vitro and in vivo models...
2018: Journal of Toxicological Sciences
Ling-Yu Li, Jia-Di Peng, Wenjuan Zhou, Hui Qiao, Xin Deng, Zhou-Hua Li, Ji-Deng Li, Yun-Dong Fu, Song Li, Kai Sun, Hong-Min Liu, Wen Zhao
Hydrazone and their derivatives are a series of highly active molecules, which are widely used as lead compounds for the research and development of new anti-cancer drugs. In this study, 20 compounds were synthesized, based on this scaffold and their in vitro cytotoxicity against 6 cancer cell lines, including EC9706, SMMC-7721, MCF7, PC3, MGC-803 and EC109 was tested. Among them, compound 6p, showed strong anti-proliferative activities on esophageal carcinoma cells: EC9706 and EC109 with IC50 values of 1...
February 14, 2018: European Journal of Medicinal Chemistry
Sanford P C Hsu, John S Kuo, Hsin-Chien Chiang, Hsin-Ell Wang, Yu-Shan Wang, Cheng-Chung Huang, Yi-Chun Huang, Mau-Shin Chi, Minesh P Mehta, Kwan-Hwa Chi
Glioblastoma (GBM) cells are characterized by high phagocytosis, lipogenesis, exocytosis activities, low autophagy capacity and high lysosomal demand are necessary for survival and invasion. The lysosome stands at the cross roads of lipid biosynthesis, transporting, sorting between exogenous and endogenous cholesterol. We hypothesized that three already approved drugs, the autophagy inducer, sirolimus (rapamycin, Rapa), the autophagy inhibitor, chloroquine (CQ), and DNA alkylating chemotherapy, temozolomide (TMZ) could synergize against GBM...
January 23, 2018: Oncotarget
Daria Ezeriņa, Yoko Takano, Kenjiro Hanaoka, Yasuteru Urano, Tobias P Dick
The cysteine prodrug N-acetyl cysteine (NAC) is widely used as a pharmacological antioxidant and cytoprotectant. It has been reported to lower endogenous oxidant levels and to protect cells against a wide range of pro-oxidative insults. As NAC itself is a poor scavenger of oxidants, the molecular mechanisms behind the antioxidative effects of NAC have remained uncertain. Here we show that NAC-derived cysteine is desulfurated to generate hydrogen sulfide, which in turn is oxidized to sulfane sulfur species, predominantly within mitochondria...
January 29, 2018: Cell Chemical Biology
Jiaqiao Wang, Yanhua Xu, Huihui Wan, June Hu
Mitochondria has been a promising target in blood cancer given their unique dependencies on mitochondrial functions compared to normal hematopoietic cells. In line with this concept, we show that an anthelminthic drug ivermectin selectively kills chronic myeloid leukemia (CML) cells via inducing mitochondrial dysfunctions and oxidative stress. Ivermectin is significantly more effective in inducing caspase-dependent apoptosis in CML cell line K562 and primary CML CD34 than normal bone marrow (NBM) CD34 cells...
February 8, 2018: Biochemical and Biophysical Research Communications
Yao Xu, Yong Li, Limei Ma, Guang Xin, Zeliang Wei, Zhi Zeng, Zhihua Xing, Shiyi Li, Hai Niu, Wen Huang
Cataract is the leading cause of blindness with an estimated 16 million people affected worldwide. d-Galactose (d-gal) is a reducing sugar that widely distributed in foodstuffs, and studies show that d-gal could promote cataract formation by damaging nature lens epithelial cells (LECs). However, the underlying mechanism is unclear. In our present study, d-gal resulted in premature senescence of LECs, which was confirmed by determining the β-galactosidase activity, cell proliferative potential and cell cycle distribution, though apoptosis of LECs was not observed...
February 6, 2018: Toxicology Letters
Xiaoting Jin, Ruijun Su, Ruijin Li, Long Cheng, Zhuoyu Li
Fine particulate matter exposure may cause health risk, including cardiovascular diseases and cancer. Bone marrow mesenchymal stem cell (BMSC), a typical model for evaluating pollutant toxicity, has been closely linked to these diseases, due to its characteristics of differentiation. We therefore studied the BMSCs differentiation and its roles in inflammatory activation in the respiratory tract upon PM2.5 exposure using both in vitro and in vivo models. BMSCs differentiation into endothelial-like cells (ELCs) and cancer-associated fibroblasts cells (CAFs) was enhanced in response to conditioned medium from PM2...
January 5, 2018: Oncotarget
Miao Li, Jian Li, Jianling Yang, Jianguo Liu, Zhengzheng Zhang, Xiaotian Song, Zhiyan Yao, Cuiqing Ma, Wenjian Li, Ruihong Zeng, Kai Wang, Lin Wei
Respiratory syncytial virus (RSV) is the main cause of acute lower respiratory tract infection (ALRI) in children worldwide. Virus-host interaction affects progression and prognosis of the infection. Autophagy plays important roles in virus-host interaction. Respiratory epithelial cells serve as the front line of host defense during RSV infection, However, it is still unclear how they interact with RSV. In this study, We found that RSV induced autophagy which favored RSV replication and exacerbated lung pathology in vivo Mechanistically, RSV induced complete autophagy flux through Reactive oxygen species (ROS) generation and activation of AMPK-MTOR (AMP-activated protein kinase/mammalian target of rapamycin) signaling pathway in Hep2 cells...
January 31, 2018: Journal of Virology
Guoyong Jiang, Lulu Zhang, Hui Wang, Qian Chen, Xiaolin Wu, Xiaoli Yan, Yi Chen, Mingyong Xie
The preventive role of a purified Ganoderma atrum polysaccharide PSG-1-F2 as a new dietary antioxidant against the intestinal toxicity of acrylamide (ACR) was investigated in vitro. Our results showed that ACR could induce oxidative stress in IEC-6 cells by the overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and as well as the reduction in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In addition, the induction of a mitochondria-mediated intrinsic apoptotic pathway by ACR was evidenced by the events of loss of mitochondrial membrane potential, bax/bcl-2 dysregulation, cytochrome c release, and activation of caspase-3...
January 24, 2018: Food & Function
Yuxia Liu, Bin Yang, Lirong Zhang, Xianling Cong, Zhen Liu, Yu Hu, Jing Zhang, Haixia Hu
Presently, developing effective anti-colon cancer drugs still remains to be important. Ginkgolic acids (GA), as a botanical drug extracted from the seed coat of Ginkgo biloba L., possess various bioactive properties. Our findings, for the first time, indicated that GA suppressed colon cancer cell proliferation, migration and invasion. GA led to cell death through G0/G1 phase arrest. In addition, apoptosis was significantly induced by GA treatment. The intrinsic apoptosis pathway was included, proved by the release of cytochrome c (Cyto-c) from the mitochondria into the cytosol...
January 15, 2018: Biochemical and Biophysical Research Communications
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
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...
March 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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...
February 1, 2018: Toxicology
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
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 through 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...
January 2018: Free Radical Research
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
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...
January 2018: Food and Chemical Toxicology
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
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