引文著录:
杨凤娟, 谭宁, 张天禹, 程潭. 谷胱甘肽在肿瘤细胞发生铁死亡过程中的作用研究.
世界华人消化杂志
2021; 29(15): 901-907
Role of glutathione in ferroptosis of tumor cells
Feng-Juan Yang, Ning Tan, Tian-Yu Zhang, Tan Cheng
Feng-Juan Yang, Tan Cheng,
Department of Human Anatomy, Basic Medical College, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China
Ning Tan,
Scientific Experiment Center, Department of Human Anatomy, Basic Medical College Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China
Tian-Yu Zhang,
Department of Urology, the Affiliated Hospital, Guilin Medical University, Guilin 541004, Guangxi Zhuang Autonomous Region, China
Supported by
:
Regional Fund Project of National Natural Science Foundation of China
, No.
81360326 and No. 81360377
;
Key Projects of Guangxi Natural Science Foundation
, No.
2015GXNSFDA139027
.
Corresponding author
: Tan Cheng, PhD, Attending Physician, Department of Human Anatomy, Basic Medical College, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China.
chengt2080@glmc.edu.cn
Received:
April 9, 2021
Revised:
May 18, 2021
Accepted:
June 18, 2021
Published online:
August 8, 2021
Ferroptosis is a type of iron-dependent lipid peroxidation and reactive oxygen species (ROS)-induced regulatory cell death discovered in recent years, which is accompanied by the increase of ROS level and the decrease of antioxidant system components, such as glutathione peroxidase in enzyme antioxidants and glutathione in non-enzyme antioxidants. Glutathione (GSH) is the predominant low-molecular-weight antioxidant with a ubiquitous distribution inside the cell, and its steady-state level depends on the absorption rate of amino acid precursors, enzyme activity, recovery of glutathione disulfide, and the balance between oxidation and reduction. At present, targeted glutathione metabolism has been used in cancer treatment widely. Compared with combination therapy, GSH depletion as a single treatment strategy has a significant effect. Therefore, further understanding of the role of GSH in ferroptosis will provide new ideas and directions for cancer treatment.
Dolma S
, Lessnick SL, Hahn WC, Stockwell BR. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.
Cancer Cell
. 2003;
3
:285-296.
[
PubMed
]
[
DOI
]
Yang WS
, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells.
Chem Biol
. 2008;
15
:234-245.
[
PubMed
]
[
DOI
]
Dixon SJ
, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death.
Cell
. 2012;
149
:1060-1072.
[
PubMed
]
[
DOI
]
Desideri E
, Ciccarone F, Ciriolo MR. Targeting Glutathione Metabolism: Partner in Crime in Anticancer Therapy.
Nutrients
. 2019;11.
[
PubMed
]
[
DOI
]
Hanschmann EM
, Godoy JR, Berndt C, Hudemann C, Lillig CH. Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling.
Antioxid Redox Signal
. 2013;
19
:1539-1605.
[
PubMed
]
[
DOI
]
Manz DH
, Blanchette NL, Paul BT, Torti FM, Torti SV. Iron and cancer: recent insights.
Ann NY Acad Sci
. 2016;
1368
:149-161.
[
PubMed
]
[
DOI
]
Lewerenz J
, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M, Smith SB, Ganapathy V, Maher P. The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities.
Antioxid Redox Signal
. 2013;
18
:522-555.
[
PubMed
]
[
DOI
]
Yang WS
, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, Brown LM, Girotti AW, Cornish VW, Schreiber SL, Stockwell BR. Regulation of ferroptotic cancer cell death by GPX4.
Cell
. 2014;
156
:317-331.
[
PubMed
]
[
DOI
]
Kagan VE
, Mao G, Qu F, Angeli JP, Doll S, Croix CS, Dar HH, Liu B, Tyurin VA, Ritov VB, Kapralov AA, Amoscato AA, Jiang J, Anthonymuthu T, Mohammadyani D, Yang Q, Proneth B, Klein-Seetharaman J, Watkins S, Bahar I, Greenberger J, Mallampalli RK, Stockwell BR, Tyurina YY, Conrad M, Bayır H. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis.
Nat Chem Biol
. 2017;
13
:81-90.
[
PubMed
]
[
DOI
]
Doll S
, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, Goya Grocin A, Xavier da Silva TN, Panzilius E, Scheel CH, Mourão A, Buday K, Sato M, Wanninger J, Vignane T, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O'Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli JPF, Conrad M. FSP1 is a glutathione-independent ferroptosis suppressor.
Nature
. 2019;
575
:693-698.
[
PubMed
]
[
DOI
]
Bersuker K
, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, Bassik MC, Nomura DK, Dixon SJ, Olzmann JA. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.
Nature
. 2019;
575
:688-692.
[
PubMed
]
[
DOI
]
Angeli JPF
, Shah R, Pratt DA, Conrad M. Ferroptosis Inhibition: Mechanisms and Opportunities.
Trends Pharmacol Sci
. 2017;
38
:489-498.
[
PubMed
]
[
DOI
]
Espinosa-Diez C
, Miguel V, Mennerich D, Kietzmann T, Sánchez-Pérez P, Cadenas S, Lamas S. Antioxidant responses and cellular adjustments to oxidative stress.
Redox Biol
. 2015;
6
:183-197.
[
PubMed
]
[
DOI
]
Wu G
, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health.
J Nutr
. 2004;
134
:489-492.
[
PubMed
]
[
DOI
]
Bansal A
, Simon MC. Glutathione metabolism in cancer progression and treatment resistance.
J Cell Biol
. 2018;
217
:2291-2298.
[
PubMed
]
[
DOI
]
Lu H
, Samanta D, Xiang L, Zhang H, Hu H, Chen I, Bullen JW, Semenza GL. Chemotherapy triggers HIF-1-dependent glutathione synthesis and copper chelation that induces the breast cancer stem cell phenotype.
Proc Natl Acad Sci USA
. 2015;
112
:E4600-E4609.
[
PubMed
]
[
DOI
]
Lopes-Coelho F
, Gouveia-Fernandes S, Gonçalves LG, Nunes C, Faustino I, Silva F, Félix A, Pereira SA, Serpa J. HNF1β drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC).
Tumour Biol
. 2016;
37
:4813-4829.
[
PubMed
]
[
DOI
]
Ke HL
, Lin J, Ye Y, Wu WJ, Lin HH, Wei H, Huang M, Chang DW, Dinney CP, Wu X. Genetic Variations in Glutathione Pathway Genes Predict Cancer Recurrence in Patients Treated with Transurethral Resection and Bacillus Calmette-Guerin Instillation for Non-muscle Invasive Bladder Cancer.
Ann Surg Oncol
. 2015;
22
:4104-4110.
[
PubMed
]
[
DOI
]
Li B
, Qiu B, Lee DS, Walton ZE, Ochocki JD, Mathew LK, Mancuso A, Gade TP, Keith B, Nissim I, Simon MC. Fructose-1,6-bisphosphatase opposes renal carcinoma progression.
Nature
. 2014;
513
:251-255.
[
PubMed
]
[
DOI
]
Wang W
, Kryczek I, Dostál L, Lin H, Tan L, Zhao L, Lu F, Wei S, Maj T, Peng D, He G, Vatan L, Szeliga W, Kuick R, Kotarski J, Tarkowski R, Dou Y, Rattan R, Munkarah A, Liu JR, Zou W. Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer.
Cell
. 2016;
165
:1092-1105.
[
PubMed
]
[
DOI
]
Harris IS
, Treloar AE, Inoue S, Sasaki M, Gorrini C, Lee KC, Yung KY, Brenner D, Knobbe-Thomsen CB, Cox MA, Elia A, Berger T, Cescon DW, Adeoye A, Brüstle A, Molyneux SD, Mason JM, Li WY, Yamamoto K, Wakeham A, Berman HK, Khokha R, Done SJ, Kavanagh TJ, Lam CW, Mak TW. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression.
Cancer Cell
. 2015;
27
:211-222.
[
PubMed
]
[
DOI
]
Rocha CR
, Garcia CC, Vieira DB, Quinet A, de Andrade-Lima LC, Munford V, Belizário JE, Menck CF. Glutathione depletion sensitizes cisplatin- and temozolomide-resistant glioma cells in vitro and in vivo.
Cell Death Dis
. 2015;
6
:e1727.
[
PubMed
]
[
DOI
]
Fath MA
, Ahmad IM, Smith CJ, Spence J, Spitz DR. Enhancement of carboplatin-mediated lung cancer cell killing by simultaneous disruption of glutathione and thioredoxin metabolism.
Clin Cancer Res
. 2011;
17
:6206-6217.
[
PubMed
]
[
DOI
]
Tagde A
, Singh H, Kang MH, Reynolds CP. The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma.
Blood Cancer J
. 2014;
4
:e229.
[
PubMed
]
[
DOI
]
Robe PA
, Martin DH, Nguyen-Khac MT, Artesi M, Deprez M, Albert A, Vanbelle S, Califice S, Bredel M, Bours V. Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults.
BMC Cancer
. 2009;
9
:372.
[
PubMed
]
[
DOI
]
Lee YS
, Lee DH, Jeong SY, Park SH, Oh SC, Park YS, Yu J, Choudry HA, Bartlett DL, Lee YJ. Ferroptosis-inducing agents enhance TRAIL-induced apoptosis through upregulation of death receptor 5.
J Cell Biochem
. 2019;
120
:928-939.
[
PubMed
]
[
DOI
]
Kerins MJ
, Milligan J, Wohlschlegel JA, Ooi A. Fumarate hydratase inactivation in hereditary leiomyomatosis and renal cell cancer is synthetic lethal with ferroptosis induction.
Cancer Sci
. 2018;
109
:2757-2766.
[
PubMed
]
[
DOI
]
Pan X
, Lin Z, Jiang D, Yu Y, Yang D, Zhou H, Zhan D, Liu S, Peng G, Chen Z, Yu Z. Erastin decreases radioresistance of NSCLC cells partially by inducing GPX4-mediated ferroptosis.
Oncol Lett
. 2019;
17
:3001-3008.
[
PubMed
]
[
DOI
]
Joyce-Brady M
, Hiratake J. Inhibiting Glutathione Metabolism in Lung Lining Fluid as a Strategy to Augment Antioxidant Defense.
Curr Enzym Inhib
. 2011;
7
:71-78.
[
PubMed
]
[
DOI
]
Zhao Y
, Seefeldt T, Chen W, Carlson L, Stoebner A, Hanson S, Foll R, Matthees DP, Palakurthi S, Guan X. Increase in thiol oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to X-ray irradiation.
Free Radic Biol Med
. 2009;
47
:176-183.
[
PubMed
]
[
DOI
]
Montero AJ
, Diaz-Montero CM, Deutsch YE, Hurley J, Koniaris LG, Rumboldt T, Yasir S, Jorda M, Garret-Mayer E, Avisar E, Slingerland J, Silva O, Welsh C, Schuhwerk K, Seo P, Pegram MD, Glück S. Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer.
Breast Cancer Res Treat
. 2012;
132
:215-223.
[
PubMed
]
[
DOI
]
Munoz M
, Henderson M, Haber M, Norris M. Role of the MRP1/ABCC1 multidrug transporter protein in cancer.
IUBMB Life
. 2007;
59
:752-757.
[
PubMed
]
[
DOI
]
Cao JY
, Poddar A, Magtanong L, Lumb JH, Mileur TR, Reid MA, Dovey CM, Wang J, Locasale JW, Stone E, Cole SPC, Carette JE, Dixon SJ. A Genome-wide Haploid Genetic Screen Identifies Regulators of Glutathione Abundance and Ferroptosis Sensitivity.
Cell Rep
. 2019;
26
:1544-1556.e8.
[
PubMed
]
[
DOI
]
Desideri E
, Filomeni G, Ciriolo MR. Glutathione participates in the modulation of starvation-induced autophagy in carcinoma cells.
Autophagy
. 2012;
8
:1769-1781.
[
PubMed
]
[
DOI
]
