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| 1 | Th e role of ferroptosis in ionizing radiation-induced cell death and tumor suppression显示文摘Ferroptosis,a form of regulated cell death caused by lipid peroxidation,was recently identified as a natural tumor suppression mechanism.Here,we show that ionizing radiation(IR)induces ferroptosis in cancer cells.Mechanistically,IR induces not only reactive oxygen species(ROS)but also the expression of ACSL4,a lipid metabolism enzyme required for ferroptosis,resulting in elevated lipid peroxidation and ferroptosis.ACSL4 ablation largely abolishes IR-induced ferroptosis and promotes radioresistance.IR also induces the expression of ferroptosis inhibitors,including SLC7A11 and GPX4;as an adaptive response.IR-or KEAP1 deficiencyinduced SLC7A11 expression promotes radioresistance through inhibiting ferroptosis.Inactivating SLC7A11 or GPX4 with ferroptosis inducers(FINs)sensitizes radioresistant cancer cells and xenograft tumors to IR.Furthermore,radiotherapy induces ferroptosis in cancer patients,and increased ferroptosis correlates with better response and longer survival to radiotherapy in cancer patients.Our study reveals a previously unrecognized link between IR and ferroptosis and indicates that further exploration of the combination of radiotherapy and FINs in cancer treatment is warranted. | Guang Lei Yilei Zhang Pranavi Koppula Xiaoguang Liu Jie Zhang Steven HLin Jaffer AAjani Qin Xiao Zhongxing Liao Hui Wang Boyi Gan | 2020 | Cell Research2020，30，2： | 88 |
| 2 | 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 |
| 3 | 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 |
| 4 | Cytochrome P450 reductase(POR)as a ferroptosis fuel显示文摘Oxygen,iron,and polyunsaturated fatty acids(PUFAs;fatty acids containing more than one double bond)are all beneficial to our cellular lives.Incorporation of these components into cellular processes,however,comes at a cost:the bis-allylic structure of PUFAs and the enrichment of cellular environments with iron and oxygen render PUFA-containing phospholipids(PUFA-PLs)particularly susceptible to peroxidation(Yang and Stockwell,2016). | Pranavi Koppula Li Zhuang Boyi Gan | 2021 | Protein & Cell2021，12，9： | 2 |
| 5 | Chrysanthemum indicum ethanol extract attenuates hepatic stellate cell activation in vitro and thioacetamide-induced hepatofibrosis in rats显示文摘Objective:To investigate the antifibrotic effects of Chrysanthemum indicum ethanol extract(CIEE)against activated hepatic stellate cells(HSC)and thioacetamide(TAA)-induced hepatofibrosis in rats.Methods:Cell viability and proliferation of HSC-T6 cells were measured using MTT assay.Primary HSCs were used to study morphology.TAA(200 mg/kg)was used to induced hepatic fibrosis in rats.CIEE(100 and 500 mg/kg)and silymarin(50 mg/kg)were administered orally.Liver functions including alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels were measured using commercial kits.Liver sections and fibrotic biomarker expression were measured using hematoxylin and eosin staining and real-time polymerase chain reaction.Results:In vitro study revealed that CIEE(0.1,0.25,and 0.5 mg/mL)inhibited the proliferation of activated HSCs exposed to transforming growth factor(TGF)-β and restored the activated primary HSC morphology.In in vivo studies,TAA-induced increase in liver/body weight ratio(5.46±0.26)was significantly reduced(4.13±0.22)by CIEE(P<0.05 at 500 mg/kg).CIEE(100 and 500 mg/kg)improved the liver functions by significantly attenuating changes in alanine transaminase,aspartate transaminase,glutathione,and hydroxyproline levels(P<0.05).Further,CIEE(100 and 500 mg/kg)ameliorated the histological changes in liver tissue and TGF-β expression significantly(P<0.05)in TAA-induced rats.Conclusions:CIEE significantly protects against TAA-induced liver damage in rats and can be used in the treatment of liver fibrosis. | Yun-Jin Chae Sushruta Koppula Myong-Ki Kim Tony Yoon MinDong Song | 2021 | Asian Pacific Journal of Tropical Biomedicine2021，11，11： | 2 |
| 6 | Oxidation of sulfur dioxide to sulfur trioxide over supported vanadia catalysts 显示文摘 | Dunn J P Koppula P R Stenger H G | 1998 | Applied Catalysis B1998，19，： | 1 |
| 7 | Recent developments in the inhibitors of neuroinflammation and nearodegeneration:inflammatory oxidative enzymes as drug target 显示文摘 | CHOI D K KOPPULA S CI-IOI M | 2010 | Expert opinion therapeutic patents2010，20，11： | 1 |
| 8 | Chrysanthemum morifolium Ramat(CM)extract protects human neuroblastoma SH- SY5Y ceils against MPP+induced cytotoxicity显示文摘 | Kim I S Koppula S Park P J | 2009 | Journal of Ethnopharmacology2009，126，3： | 1 |
| 9 | Serum albumin levels in ischemic stroke and its subtypes: Correlation with clinical outcome显示文摘 | Mallemoggala Sai Babu Subhash Kaul Sneha Dadheech Koppula Rajeshwar Akka Jyothy Anjana Munshi | 2013 | Nutrition2013，，6： | 1 |
| 10 | Inhibitors of microglial neurotoxicity: focus on natural products显示文摘 | Choi DK Koppula S Suk K | 2011 | Molecules2011，16，2： | 1 |
| 11 | Protective effect of Chrysanthe- mum indicum Linne against 1-methyl-4-phenylpridiniurn ion and li- popolysaccharide-induced cytotoxicity in cellular model of Parkinson's disease显示文摘 | KIM I S KO H M KOPPULA S | 2011 | Food and Chemical Toxicology2011，49，14： | 1 |
| 12 | BT-11 is effective for enhancing cognitive functions in the elderly humans显示文摘 | Ki Young Shin Jun-Young Lee Beom Young Won Hee Yeon Jung Keun-A. Chang Sushruta Koppula Yoo-Hun Suh | 2009 | Neuroscience Letters2009，，2： | 1 |
| 13 | The melanocorfin receptors : agonists, antagonists, and the hormonal control of pigmenta- tion 显示文摘 | Cone R D Lu D Koppula S | 1996 | Recent Prog Horm Res1996，51，31： | 1 |
| 14 | Catpesiam n:croce:am : lipopolysaccharide- induced inflammation in maerophages by regulating the NF-KB/IKB-et, Akt, and STAT signaling Pathways 显示文摘 | Koppula S Kim WJ Jiaag J | 2013 | Am J Chin Med2013，41，4： | 1 |
| 15 | Oxidation of sulfur dioxide to sulfur trioxide over supported vanadia catalysts显示文摘 | DUNN J P KOPPULA P R STENGER H G | 1998 | Appl Catal B: Environ1998，19，2： | 1 |
| 16 | Imaging of multiple myeloma: usefulness, of MRI and PET/CT 显示文摘 | Koppula B Kaptucb J Hanrahan CJ | 2013 | Semin Ultra- sound CT MR2013，34，6： | 1 |
| 17 | Recent developmentsin the inhibitors of neuroinflammation and neurodegenera-tion: inflammatory oxidative enzymes as a drug target 显示文摘 | Choi DK* Koppula S Choi M | 2010 | Expert Opin Ther Pat2010，，11： | 1 |
| 18 | Oxidationof sulfur dioxide to sulfur trioxide over supported vanadia cata-lysts显示文摘 | DUNN J P KOPPULA P R STENGER H G | 1998 | Applied Catalysis B:Environmental1998，19，2： | 1 |
| 19 | Regulation of Microglia Activity by Glaucocalyxin-A: Attenuation of Lipopolysaccharlde- Stimulated Neuroinflammation through NF-KB and p38 MAPK Signaling Pathways 显示文摘 | Kim BW Koppula S Hang SS | | PLoS One0，8，55： | 1 |
| 20 | Oxidation of sulfur dioxide to sulfur trioxide over supported vanadia catalysts显示文摘 | Dunn J P Koppula P R G Stenger H | 1998 | Applied Catalysis B: Environmental1998，19，2： | 1 |
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