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| 1 | Cystine transporter SLC7A11/xCT in cancer:ferroptosis,nutrient dependency,and cancer therapy显示文摘The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) cancer.In this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies. | Pranavi Koppula Li Zhuang Boyi Gan | 2021 | Protein & Cell2021，12，8： | 97 |
| 2 | Amino acid transporter SLC7A11/ xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer显示文摘Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment. | Pranavi Koppula Yilei Zhang Li Zhuang Boyi Gan | 2018 | Cancer Communications2018，38，1： | 77 |
| 3 | NADPH debt drives redox bankruptcy:SLC7A11/xCT-mediated cystine uptake as a double-edged sword in cellular redox regulation显示文摘Cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT)plays a key role in antioxidant defense by mediating cystine uptake,promoting glutathione synthesis,and maintaining cell survival under oxidative stress conditions.Recent studies showed that,to prevent toxic buildup of highly insoluble cystine inside cells,cancer cells with high expression of SLC7A11(SLC7A11high)are forced to quickly reduce cystine to more soluble cysteine,which requires substantial NADPH supply from the glucose-pentose phosphate pathway(PPP)route,thereby inducing glucose-and PPP-dependency in SLC7A11high cancer cells.Limiting glucose supply to SLC7A11high cancer cells results in significant NADPH“debt”,redox“bankruptcy”,and subsequent cell death.This review summarizes our current understanding of NADPH-generating and-consuming pathways,discusses the opposing role of SLC7A11 in protecting cells from oxidative stresseinduced cell death such as ferroptosis but promoting glucose starvationeinduced cell death,and proposes the concept that SLC7A11-mediated cystine uptake acts as a double-edged sword in cellular redox regulation.A detailed understanding of SLC7A11 in redox biology may identify metabolic vulnerabilities in SLC7A11high cancer for therapeutic targeting. | Xiaoguang Liu Yilei Zhang Li Zhuang Kellen Olszewski Boyi Gan | 2021 | Genes & Diseases2021，8，6： | 7 |
| 4 | Synthesis of cystine C_(60) derivative and its protective effects on hydrogen peroxide-induced apoptosis in PC12 cells显示文摘Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities, especially prominent in neural diseases. One of the usable ways to prevent the reactive oxygen species (ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of some free radical scavenger. Water-soluble amino-fullerene is a novel compound that behaves as a free radical scavenger with excellent biology consistent. In the present study, we have synthesized and characterized a novel cystine C60 derivative for the first time, and investigated the effects on hydrogen peroxide-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with hydrogen peroxide underwent apoptotic death as determined by MTT, PI/Hoechst 33342 staining and flow cytometry analysis. These results suggested that cystine C60 derivative has the potential to prevent oxidative stress-induced cell death and has no evident toxicity. | Zhen Hu, Hai Ping Xing, Zhou Zhu, Wei Wang, Wen Chao Guan Department of Chemistry, Huazhong University of Science and Technology, Wuhan 430074, China Department of Neurology, Tongji Hospital, Tongji Medical College, Wuhan 430030, China | 2007 | Chinese Chemical Letters2007，18，2： | 2 |
| 5 | Cystine supplementation rebalances the redox homeostasis of microenvironment in non-small cell lung cancer cells and reverses their resistance to docetaxel显示文摘Continuous docetaxel(DTX)treatment of non-small cell lung cancer induces development of drug resistance,but the mechanism is poorly understood.In this study we performed metabolomics analysis to characterize the metabolic patterns of sensitive and resistant A549 non-small cell lung cancer cells(A549/DTX cells).We showed that the sensitive and resistant A549 cells exhibited distinct metabolic phenotypes:the resistant cells were characterized by an altered microenvironment of redox homeostasis with reduced glutathione and elevated reactive oxygen species(ROS).DTX induction reprogrammed the metabolic phenotype of the sensitive cells,which acquired a phenotype similar to that of the resistant cells:it reduced cystine influx,inhibited glutathione biosynthesis,increased ROS and decreased glutathione/glutathione disulfide(GSH/GSSG);the genes involved in glutathione biosynthesis were dramatically depressed.Addition of the ROS-inducing agent Rosup(25,50μg/mL)significantly increased P-glycoprotein expression and reduced intracellular DTX in the sensitive A549 cells,which ultimately acquired a phenotype similar to that of the resistant cells.Supplementation of cystine(1.0 mM)significantly increased GSH synthesis,rebalanced the redox homeostasis of A549/DTX cells,and reversed DTX-induced upregulation of P-glycoprotein,and it markedly improved the effects of DTX and inhibited the growth of A549/DTX in vitro and in vivo.These results suggest that microenvironmental redox homeostasis plays a key role in the acquired resistance of A549 cancer cells to DTX.The enhancement of GSH synthesis by supplementary cystine is a promising strategy to reverse the resistance of tumor cells and has potential for translation in the clinic. | Si-jia Li Bei Cao Zhen-yao Lu Run-bin Sun Su-han Guo Yuan Xie Ji-ye Aa Guang-ji Wang | 2021 | Acta Pharmacologica Sinica2021，42，12： | 1 |
| 6 | AN FTIR SPECTROSCOPIC STUDY OF LOW TEMPERATURE PLASMA TREATED WOOL FABRIC显示文摘FTIR-ATR technique with second-order derivative measurement was used for assessing the amount of oxidation products of cystine present on the plasma-treated wool fabric surface. In this paper, three non-polymerising gases namely oxygen, nitrogen and 25% hydrogen/75% nitrogen gas mixture were used for the plasma treatment of wool fabric. The oxidation products of cystine studied included S-sulphonate, cysteic acid, cystine monoxide and cystine dioxide. The variations of the amount of these products as a function of treatment time were studied. Experimental results showed that the oxygen plasma could produce a large amount of oxidation products of cystine on the wool fabric surface followed by nitrogen plasma and gas mixture plasma. | 简志伟 陈光 袁俊华 苗孟河 | 1997 | Journal of China Textile University(English Edition)1997，14，3： | 0 |
| 7 | Quantitative determination of D_(4)-cystine in mice using LC-MS/MS and its application to the assessment of pharmacokinetics and bioavailability显示文摘Cystine is the primary source material for the synthesis of glutathione.However,the pharmacokinetics and tissue distribution of cystine are largely unknown.A surrogate analyte D_(4)-cystine was employed to generate calibration curves for the determination of levels of D_(4)-cystine and endogenous cystine in mice by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Validation assessments proved the sensitivity,specificity and reproducibility of the method with a lower limit of quantification(LLOQ)of 5 ng/mL over 5e5000 ng/mL in plasma.The pharmacokinetics of D_(4)-cystine were evaluated after administering injections and oral solutions,both of which minimally impacted endogenous cystine levels.The absolute bioavailability of cystine was 18.6%,15.1%and 25.6%at doses of 25,50 and 100 mg/kg,respectively.Intravenously injected D_(4)-cystine resulted in dramatically high plasma levels with reduced levels in the brain and liver.Intragastrically administered D_(4)-cystine resulted in high levels in the plasma and stomach with relatively low levels in the lung,kidney,heart and brain. | Shuning Li Zhenyao Lu Li Jiao Ran Zhang Yu Hong Jiye Aa Guangji Wang | 2021 | Journal of Pharmaceutical Analysis2021，11，5： | 0 |
| 8 | Cystine-assisted accumulation of gold nanoparticles on ZnO to construct a sensitive surface-enhanced Raman spectroscopy substrate显示文摘Recently,various semiconductor/metal composites have been developed to fabricate surfaceenhanced Raman spectroscopy substrates.However,low metal loading on semiconductors is still a challenge.In this study,cystine was introduced to increase the accumulation of gold nanoparticles on zinc oxide,owing to the biomineralization_property of_cystine.Morphological analysis revealed that the obtained ZnO/Au/cystine composite not only had a higher metal loading but also formed a porous structure,which is beneficial for Raman performance.Compared with ZnO/Au,the ZnO/Au/cystine substrate displayed a 40-fold enhancement in the Raman signal and a lower limit of detection(10^(-11) mol·L^(-1))in the detection of rhodamine 6G.Moreover,the substrate has favorable homogeneity and stability.Finally,ZnO/Au/cystine displayed excellent performance toward crystal violet and methylene blue in a test based on river water samples.This study provided a promising method to fabricate sensitive semiconductor/noblemetal-based surface-enhanced Ramans spectroscopy substrates for Raman detection. | Qi Qu Chuan Zeng Jing Huang Mengfan Wang Wei Qi Zhimin He | 2023 | Frontiers of Chemical Science and Engineering2023，17，1： | 0 |
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