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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

Role of Nuclear Factor Erythroid 2-Related Factor 2 (NRF-2) Mediated Antioxidant Response on the Synergistic Antitumor Effect of L-Arginine and 5-Fluro Uracil (5FU) in Breast Adenocarcinoma

Author(s): Asis Bala* and Shravani Sripathi Panditharadyula

Volume 25 , Issue 14 , 2019

Page: [1643 - 1652] Pages: 10

DOI: 10.2174/1381612825666190705205155

Price: $65

Abstract

Breast adenocarcinoma (BAC) in glandular tissue cells have excessive metastasis and invasion capability. The major challenges for the chemotherapy used for the management of BAC include chemoresistance and auto-immunosuppression in BAC. The 5-fluro uracil (5-FU) based therapy promotes the immune activation in BAC by targeting the regulatory T cells and myeloid-derived suppressor cells (MDSC). The beneficial effect of the combination of L-Arginine with 5-FU strives to be established in different pre-clinical and clinical conditions and explored in the scientific literature. L-Arginine induces NO production and potentiates the anticancer effect of 5-FU. NO-mediated signaling is regulated by nuclear factor erythroid 2-related factor 2 (NRF-2) mediated antioxidant response. NRF-2 mediated antioxidant mechanism always suppresses the formation of superoxide (O2 -) as well as other reactive oxygen species (ROS). Thus the utilization of NO by O2 - will be minimum in this combination therapy. The regulatory role of NRF-2 in regulation to Antioxidant Response Element (ARE) mediated cytoprotective gene expression in BAC remains unexplored. The present review summarizes the role of NRF-2 mediated antioxidant response on the synergistic antitumor effect of L-Arginine and 5-FU in BAC. This review brought new insight into the management of BAC and in the same context, a hypothesis is raised on the use of reduced glutathione (GSH) or N-Acetyl Cysteine as it may be an added adjuvant in the combination of 5- FU and L-Arginine for management of BAC.

Keywords: Nuclear factor erythroid 2-related factor 2 (NRF-2), 5-fluro uracil, L-arginine, chemo-resistance, immunopharmacology, breast adenocarcinoma.

[1]
Saijo N. Progress in cancer chemotherapy with special stress on molecular-targeted therapy. Jpn J Clin Oncol 2010; 40(9): 855-62. [http://dx.doi.org/10.1093/jjco/hyq035]. [PMID: 20651047].
[2]
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45(2): 228-47. [http://dx.doi.org/10.1016/j.ejca.2008.10.026]. [PMID: 19097774].
[3]
Ke X, Shen L. Molecular targeted therapy of cancer: The progress and future prospect. Frontiers Lab Med 2017; 1: 69-75. [http://dx.doi.org/10.1016/j.flm.2017.06.001].
[4]
Kufe DW, Pollock RE, Ralph RW, et al. Holland- Frei cancer medicine. 2003; 10: 1-55009-213-8.
[5]
Tosi D, Pérez-Gracia E, Atis S, et al. Rational development of synergistic combinations of chemotherapy and molecular targeted agents for colorectal cancer treatment. BMC Cancer 2018; 18(1): 812. [http://dx.doi.org/10.1186/s12885-018-4712-z]. [PMID: 30103709].
[6]
Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: The beginning of the end of cancer? BMC Med 2016; 14: 73. [http://dx.doi.org/10.1186/s12916-016-0623-5]. [PMID: 27151159].
[7]
Bala A, Mukherjee PK, Braga FC, et al. Comparative inhibition of MCF-7 breast cancer cell growth, invasion and angiogenesis by Cannabis sativa L. sourced from sixteen different geographic locations. S Afr J Bot 2018; 119: 154-62. [http://dx.doi.org/10.1016/j.sajb.2018.07.022].
[8]
Bala A, Motlalepula G. Matsabisa, et al Possible importance of Cannabis sativa L. in regulation of insulin and IL-6R/MAO-A in cancer cell progression and migration of breast cancer patients with diabetes. S Afr J Sci 2018; 114: 7-8.
[9]
Zoli W, Ulivi P, Tesei A, et al. Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines. Breast Cancer Res 2005; 7(5): R681-9. [http://dx.doi.org/10.1186/bcr1274]. [PMID: 16168113].
[10]
Sharma GN, Dave R, Sanadya J, Sharma P, Sharma KK. Various types and management of breast cancer: an overview. J Adv Pharm Technol Res 2010; 1(2): 109-26. [PMID: 22247839].
[11]
Osborne C, Wilson P, Tripathy D. Oncogenes and tumor suppressor genes in breast cancer: Potential diagnostic and therapeutic applications. Oncologist 2004; 9(4): 361-77. [http://dx.doi.org/10.1634/theoncologist.9-4-361]. [PMID: 15266090].
[12]
Wilson TR, Longley DB, Johnston PG. Chemoresistance in solid tumours. Ann Oncol 2006; 17(10)(Suppl. 10): x315-24. [http://dx.doi.org/10.1093/annonc/mdl280]. [PMID: 17018746].
[13]
Weigelt B, Peterse JL, van ’t Veer LJ. Breast cancer metastasis: Markers and models. Nat Rev Cancer 2005; 5(8): 591-602. [http://dx.doi.org/10.1038/nrc1670]. [PMID: 16056258].
[14]
Jahani M, Azadbakht M, Norooznezhad F, Mansouri K. l-arginine alters the effect of 5-fluorouracil on breast cancer cells in favor of apoptosis. Biomed Pharmacother 2017; 88: 114-23. [http://dx.doi.org/10.1016/j.biopha.2017.01.047]. [PMID: 28103504].
[15]
Yoon JH. Systemic overview of 5-FU based chemotherapy in breast cancer. Korean J Clin Oncol 2005; 1(1): 68-73.
[16]
Vásquez-Vivar J, Kalyanaraman B, Martásek P, et al. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 1998; 95(16): 9220-5. [http://dx.doi.org/10.1073/pnas.95.16.9220]. [PMID: 9689061].
[17]
Zhang N, Yin Y, Xu SJ, Chen WS. 5-Fluorouracil: Mechanisms of resistance and reversal strategies. Molecules 2008; 13(8): 1551-69. [http://dx.doi.org/10.3390/molecules13081551]. [PMID: 18794772].
[18]
Bala A, Mondal C, Haldar PK, Khandelwal B. Oxidative stress in inflammatory cells of patient with rheumatoid arthritis: Clinical efficacy of dietary antioxidants. Inflammopharmacology 2017; 25(6): 595-607. [http://dx.doi.org/10.1007/s10787-017-0397-1]. [PMID: 28929423].
[19]
Bala A, Mondal C, Haldar PK, Khandelwal B. Oxidative stress in inflammatory cells of patient with rheumatoid arthritis: Clinical efficacy of dietary antioxidants. Inflammopharmacology 2017; 25(6): 595-607. [http://dx.doi.org/10.1007/s10787-017-0397-1]. [PMID: 28929423].
[20]
Buckley BJ, Marshall ZM, Whorton AR. Nitric oxide stimulates Nrf2 nuclear translocation in vascular endothelium. Biochem Biophys Res Commun 2003; 307(4): 973-9. [http://dx.doi.org/10.1016/S0006-291X(03)01308-1]. [PMID: 12878207].
[21]
Um HC, Jang JH, Kim DH, Lee C, Surh YJ. Nitric oxide activates Nrf2 through S-nitrosylation of Keap1 in PC12 cells. Nitric Oxide 2011; 25(2): 161-8. [http://dx.doi.org/10.1016/j.niox.2011.06.001]. [PMID: 21703357].
[22]
Dhakshinamoorthy S, Porter AG. Nitric oxide-induced transcriptional up-regulation of protective genes by Nrf2 via the antioxidant response element counteracts apoptosis of neuroblastoma cells. J Biol Chem 2004; 279(19): 20096-107. [http://dx.doi.org/10.1074/jbc.M312492200]. [PMID: 14985350].
[23]
Yin XY, Jiang JM, Liu JY, Zhu JR. Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice. World J Gastroenterol 2007; 13(46): 6249-53. [http://dx.doi.org/10.3748/wjg.v13.i46.6249]. [PMID: 18069768].
[24]
Cao Y, Feng Y, Zhang Y, Zhu X, Jin F. L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivo. BMC Cancer 2016; 16: 343. [http://dx.doi.org/10.1186/s12885-016-2376-0]. [PMID: 27246354].
[25]
Akhdar H, Loyer P, Rauch C, Corlu A, Guillouzo A, Morel F. Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells. Eur J Cancer 2009; 45(12): 2219-27. [http://dx.doi.org/10.1016/j.ejca.2009.05.017]. [PMID: 19524433].
[26]
Zhang N, Yin Y, Xu SJ, Chen WS. 5-Fluorouracil: Mechanisms of resistance and reversal strategies. Molecules 2008; 13(8): 1551-69. [http://dx.doi.org/10.3390/molecules13081551]. [PMID: 18794772].
[27]
Klaassen U, Wilke H, Harstrick A, Seeber S. Fluorouracil-based combinations in the treatment of metastatic breast cancer. Oncology (Williston Park) 1998; 12(1)(Suppl. 1): 31-5. [PMID: 9516601].
[28]
Swain SM, Lippman ME, Egan EF, Drake JC, Steinberg SM, Allegra CJ. Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer. J Clin Oncol 1989; 7(7): 890-9. [http://dx.doi.org/10.1200/JCO.1989.7.7.890]. [PMID: 2661735].
[29]
Catarina A, Nuno J, Simões S. Combination Chemotherapy in Cancer: Principles, Evaluation and Drug Delivery Strategies. Current Cancer Treatment - Novel Beyond Conventional Approaches 2011; pp. 693-714. [http://dx.doi.org/10.5772/22656]
[30]
Sun J, Wei Q, Zhou Y, Wang J, Liu Q, Xu H. A systematic analysis of FDA-approved anticancer drugs. BMC Syst Biol 2017; 11(5)(Suppl. 5): 87. [http://dx.doi.org/10.1186/s12918-017-0464-7]. [PMID: 28984210].
[31]
Kinch MS. An analysis of FDA-approved drugs for oncology. Drug Discov Today 2014; 19(12): 1831-5. [http://dx.doi.org/10.1016/j.drudis.2014.08.007]. [PMID: 25172803].
[32]
Fryar-Tita EB, Das JR, Davis JH, et al. Raloxifene and selective cell cycle specific agents: a case for the inclusion of raloxifene in current breast cancer treatment therapies. Anticancer Res 2007; 27(3B): 1393-9. [PMID: 17595753].
[33]
Lundqvist EÅ, Fujiwara K, Seoud M. Principles of chemotherapy. Int J Gynaecol Obstet 2015; 131(S2)(Suppl. 2): S146-9. [http://dx.doi.org/10.1016/j.ijgo.2015.06.011]. [PMID: 26433671].
[34]
Bryce J, Boers-Doets CB. Non-rash dermatologic adverse events related to targeted therapies. Semin Oncol Nurs 2014; 30(3): 155-68. [http://dx.doi.org/10.1016/j.soncn.2014.05.003]. [PMID: 25085027].
[35]
Burtness B, Anadkat M, Basti S, et al. NCCN Task Force Report: Management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Canc Netw 2009; 7(1)(Suppl. 1): S5-S21. [http://dx.doi.org/10.6004/jnccn.2009.0074]. [PMID: 19470276].
[36]
Peuvrel L, Dréno B. Dermatological toxicity associated with targeted therapies in cancer: Optimal management. Am J Clin Dermatol 2014; 15(5): 425-44. [http://dx.doi.org/10.1007/s40257-014-0088-2]. [PMID: 25117153].
[37]
Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol 2008; 8(1): 59-73. [http://dx.doi.org/10.1038/nri2216]. [PMID: 18097448].
[38]
Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: Immunoselection and immunosubversion. Nat Rev Immunol 2006; 6(10): 715-27. [http://dx.doi.org/10.1038/nri1936]. [PMID: 16977338].
[39]
Prendergast GC, Jaffee EM. Cancer immunologists and cancer biologists: Why we didn’t talk then but need to now. Cancer Res 2007; 67(8): 3500-4. [http://dx.doi.org/10.1158/0008-5472.CAN-06-4626]. [PMID: 17413003].
[40]
Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: A common basis between tumor immunity and autoimmunity. J Immunol 1999; 163(10): 5211-8. [PMID: 10553041].
[41]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011; 144(5): 646-74. [http://dx.doi.org/10.1016/j.cell.2011.02.013]. [PMID: 21376230].
[42]
Fiaschi T, Chiarugi P. Oxidative stress, tumor microenvironment, and metabolic reprogramming: A diabolic liaison. Int J Cell Biol 2012; 2012762825 [http://dx.doi.org/10.1155/2012/762825]. [PMID: 22666258].
[43]
Vincent DT, Ibrahim YF, Espey MG, Suzuki YJ. The role of antioxidants in the era of cardio-oncology. Cancer Chemother Pharmacol 2013; 72(6): 1157-68. [http://dx.doi.org/10.1007/s00280-013-2260-4]. [PMID: 23959462].
[44]
Hu X, Xuan Y. Bypassing cancer drug resistance by activating multiple death pathways--a proposal from the study of circumventing cancer drug resistance by induction of necroptosis. Cancer Lett 2008; 259(2): 127-37. [http://dx.doi.org/10.1016/j.canlet.2007.11.007]. [PMID: 18082322].
[45]
Brasseur K, Gévry N, Asselin E. Chemoresistance and targeted therapies in ovarian and endometrial cancers. Oncotarget 2017; 8(3): 4008-42. [http://dx.doi.org/10.18632/oncotarget.14021]. [PMID: 28008141].
[46]
Singh S, Gupta AK. Nitric oxide: Role in tumour biology and iNOS/NO-based anticancer therapies. Cancer Chemother Pharmacol 2011; 67(6): 1211-24. [http://dx.doi.org/10.1007/s00280-011-1654-4]. [PMID: 21544630].
[47]
Choudhari SK, Chaudhary M, Bagde S, Gadbail AR, Joshi V. Nitric oxide and cancer: A review. World J Surg Oncol 2013; 11: 118. [http://dx.doi.org/10.1186/1477-7819-11-118]. [PMID: 23718886].
[48]
Burney S, Caulfield JL, Niles JC, Wishnok JS, Tannenbaum SR. The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat Res 1999; 424(1-2): 37-49. [http://dx.doi.org/10.1016/S0027-5107(99)00006-8]. [PMID: 10064848].
[49]
Kielbik M, Klink M, Brzezinska M, Szulc I, Sulowska Z. Nitric oxide donors: spermine/NO and diethylenetriamine/NO induce ovarian cancer cell death and affect STAT3 and AKT signaling proteins. Nitric Oxide 2013; 35: 93-109. [http://dx.doi.org/10.1016/j.niox.2013.09.001]. [PMID: 24055735].
[50]
Grisham MB, Jourd’heuil D, Wink DA. Review article: Chronic inflammation and reactive oxygen and nitrogen metabolism--implications in DNA damage and mutagenesis. Aliment Pharmacol Ther 2000; 14(S1)(Suppl. 1): 3-9. [http://dx.doi.org/10.1046/j.1365-2036.2000.014s1003.x]. [PMID: 10807397].
[51]
Perrotta C, Cervia D, Di Renzo I, et al. Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition. Front Immunol 2018; 9: 1186. [http://dx.doi.org/10.3389/fimmu.2018.01186]. [PMID: 29896202].
[52]
Kim D, Park M, Jang H, Hyun H, Lim W. Chemoresistance to 5-FU inhibited by 635 nm LED irradiation in CD133+ KB cell line. Lasers Med Sci 2018; 33(1): 57-66. [http://dx.doi.org/10.1007/s10103-017-2335-2]. [PMID: 28956217].
[53]
Zhang N, Yin Y, Xu SJ, Chen WS. 5-Fluorouracil: Mechanisms of resistance and reversal strategies. Molecules 2008; 13(8): 1551-69. [http://dx.doi.org/10.3390/molecules13081551]. [PMID: 18794772].
[54]
Jahani M, Azadbakht M, Rasouli H, et al. L-arginine/5-fluorouracil combination treatment approaches cells selectively: Rescuing endothelial cells while killing MDA-MB-468 breast cancer cells. Food Chem Toxicol 2019; 123: 399-411. [http://dx.doi.org/10.1016/j.fct.2018.11.018]. [PMID: 30423404].
[55]
Jahani M, Azadbakht M, Norooznezhad F, Mansouri K. l-arginine alters the effect of 5-fluorouracil on breast cancer cells in favor of apoptosis. Biomed Pharmacother 2017; 88: 114-23. [http://dx.doi.org/10.1016/j.biopha.2017.01.047]. [PMID: 28103504].
[56]
Thongkum A, Wu C, Li YY, et al. The combination of arginine deprivation and 5-fluorouracil improves therapeutic efficacy in argininosuccinate synthetase negative hepatocellular carcinoma. Int J Mol Sci 2017; 18(6): 1175. [http://dx.doi.org/10.3390/ijms18061175]. [PMID: 28587170].
[57]
Balmant BD, Araújo EON, Yabuki D, et al. Effects of L-Arginine Supplementation on Leukogram, Inflammatory Bowel Infiltrates and Immunoglobulins with 5-FU Use in Rats. Nutr Cancer 2018; 70(2): 249-56. [http://dx.doi.org/10.1080/01635581.2018.1424346]. [PMID: 29345500].
[58]
Karen A. Beningo. The mechanical enhancement of cancer cell invasion. 25th World Cancer Conference October 19-21, 2017; Rome, Italy. ScientificTracks Abstracts [http://dx.doi.org/10.4172/1948-5956-C1-111].
[59]
Badawoud MH, Elshal EB, Zaki AI, Amin HA. The possible protective effect of L-arginine against 5-fluorouracil-induced nephrotoxicity in male albino rats. Folia Morphol (Warsz) 2017; 76(4): 608-19. [http://dx.doi.org/10.5603/FM.a2017.0037]. [PMID: 28553862].
[60]
Leocádio PCL, Antunes MM, Teixeira LG, et al. L-arginine pretreatment reduces intestinal mucositis as induced by 5-FU in mice. Nutr Cancer 2015; 67(3): 486-93. [http://dx.doi.org/10.1080/01635581.2015.1004730]. [PMID: 25803482].
[61]
Alsan Cetin I, Atasoy BM, Cilaker S, et al. A Diet Containing Beta-Hydroxy-Beta-Methylbutyrate, L-Glutamine and L-Arginine Ameliorates Chemoradiation-Induced Gastrointestinal Injury in Rats. Radiat Res 2015; 184(4): 411-21. [http://dx.doi.org/10.1667/RR14088.1]. [PMID: 26430821].
[62]
Shariatpanahi SP, Shariatpanahi SP, Madjidzadeh K, Hassan M, Abedi-Valugerdi M. Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies. J Theor Biol 2018; 442(442): 1-10. [http://dx.doi.org/10.1016/j.jtbi.2018.01.006]. [PMID: 29337259].
[63]
Alexandrou C, Al-Aqbi SS, Higgins JA, et al. Sensitivity of Colorectal Cancer to Arginine Deprivation Therapy is Shaped by Differential Expression of Urea Cycle Enzymes. Sci Rep 2018; 8(1): 12096. [http://dx.doi.org/10.1038/s41598-018-30591-7]. [PMID: 30108309].
[64]
Deveci HA, Nazıroğlu M, Nur G. 5-Fluorouracil-induced mitochondrial oxidative cytotoxicity and apoptosis are increased in MCF-7 human breast cancer cells by TRPV1 channel activation but not Hypericum perforatum treatment. Mol Cell Biochem 2017; 439(1-2): 189-98.
[65]
Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol 2011; 5(1): 5-23. [http://dx.doi.org/10.1016/j.molonc.2010.11.003]. [PMID: 21147047].
[66]
Emens LA. Breast cancer immunobiology driving immunotherapy: Vaccines and immune checkpoint blockade. Expert Rev Anticancer Ther 2012; 12(12): 1597-611. [http://dx.doi.org/10.1586/era.12.147]. [PMID: 23253225].
[67]
Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol 2011; 5(1): 5-23. [http://dx.doi.org/10.1016/j.molonc.2010.11.003]. [PMID: 21147047].
[68]
Szende B, Tyihák E, Trézl L. Role of arginine and its methylated derivatives in cancer biology and treatment. Cancer Cell Int 2001; 1(1): 3. [http://dx.doi.org/10.1186/1475-2867-1-3]. [PMID: 11983027].
[69]
Caras I, Grigorescu A, Stavaru C, et al. Evidence for immune defects in breast and lung cancer patients. Cancer Immunol Immunother 2004; 53(12): 1146-52. [http://dx.doi.org/10.1007/s00262-004-0556-2]. [PMID: 15185014].
[70]
Konjevic G, Radenkovic S, Srdic T, et al. Association of decreased NK cell activity and IFN? expression with pSTAT dysregulation in breast cancer patients. J BUON 2011; 1 6(2): 219-26.
[71]
Gruber IV, El Yousfi S, Dürr-Störzer S, Wallwiener D, Solomayer EF, Fehm T. Down-regulation of CD28, TCR-zeta (zeta) and up-regulation of FAS in peripheral cytotoxic T-cells of primary breast cancer patients. Anticancer Res 2008; 28(2A): 779-84. [PMID: 18507020].
[72]
Chen X, Du Y, Lin X, Qian Y, Zhou T, Huang Z. CD4+CD25+ regulatory T cells in tumor immunity. Int Immunopharmacol 2016; 34: 244-9. [http://dx.doi.org/10.1016/j.intimp.2016.03.009]. [PMID: 26994448].
[73]
Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003; 9(2): 606-12. [PMID: 12576425].
[74]
Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 2009; 58(1): 49-59. [http://dx.doi.org/10.1007/s00262-008-0523-4]. [PMID: 18446337].
[75]
Tan W, Zhang W, Strasner A, et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 2011; 470(7335): 548-53. [http://dx.doi.org/10.1038/nature09707]. [PMID: 21326202].
[76]
Pockaj BA, Basu GD, Pathangey LB, et al. Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer. Ann Surg Oncol 2004; 11(3): 328-39. [http://dx.doi.org/10.1245/ASO.2004.05.027]. [PMID: 14993030].
[77]
Tringler B, Zhuo S, Pilkington G, et al. B7-h4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res 2005; 11(5): 1842-8. [http://dx.doi.org/10.1158/1078-0432.CCR-04-1658]. [PMID: 15756008].
[78]
Sadun RE, Sachsman SM, Chen X, et al. Immune signatures of murine and human cancers reveal unique mechanisms of tumor escape and new targets for cancer immunotherapy. Clin Cancer Res 2007; 13(13): 4016-25. [http://dx.doi.org/10.1158/1078-0432.CCR-07-0016]. [PMID: 17606736].
[79]
Salatino M, Dalotto-Moreno T, Rabinovich GA. Thwarting galectin-induced immunosuppression in breast cancer. OncoImmunology 2013; 2(5)e24077 [http://dx.doi.org/10.4161/onci.24077]. [PMID: 23762796].
[80]
Rabinovich GA, Croci DO. Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 2012; 36(3): 322-35. [http://dx.doi.org/10.1016/j.immuni.2012.03.004]. [PMID: 22444630].
[81]
Croci DO, Salatino M, Rubinstein N, et al. Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi’s sarcoma. J Exp Med 2012; 209(11): 1985-2000. [http://dx.doi.org/10.1084/jem.20111665]. [PMID: 23027923].
[82]
Leinonen HM, Kansanen E, Pölönen P, Heinäniemi M, Levonen AL. Role of the Keap1-Nrf2 pathway in cancer. Adv Cancer Res 2014; 122: 281-320. [http://dx.doi.org/10.1016/B978-0-12-420117-0.00008-6]. [PMID: 24974185].
[83]
Menegon S, Columbano A, Giordano S. The Dual Roles of NRF2 in Cancer. Trends Mol Med 2016; 22(7): 578-93. [http://dx.doi.org/10.1016/j.molmed.2016.05.002]. [PMID: 27263465].
[84]
Itoh K, Chiba T, Takahashi S, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 1997; 236(2): 313-22. [http://dx.doi.org/10.1006/bbrc.1997.6943]. [PMID: 9240432].
[85]
Plafker KS, Nguyen L, Barneche M, Mirza S, Crawford D, Plafker SM. The ubiquitin-conjugating enzyme UbcM2 can regulate the stability and activity of the antioxidant transcription factor Nrf2. J Biol Chem 2010; 285(30): 23064-74. [http://dx.doi.org/10.1074/jbc.M110.121913]. [PMID: 20484052].
[86]
Canning P, Sorrell FJ, Bullock AN. Structural basis of Keap1 interactions with Nrf2. Free Radic Biol Med 2015; 88: (Pt B): 101-7. [http://dx.doi.org/10.1016/j.freeradbiomed.2015.05.034]. [PMID: 26057936].
[87]
Wang XJ, Li Y, Luo L, et al. Oxaliplatin activates the Keap1/Nrf2 antioxidant system conferring protection against the cytotoxicity of anticancer drugs. Free Radic Biol Med 2014; 70: 68-77. [http://dx.doi.org/10.1016/j.freeradbiomed.2014.02.010]. [PMID: 24556415].
[88]
Nioi P, Nguyen T, Sherratt PJ, Pickett CB. The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation. Mol Cell Biol 2005; 25(24): 10895-906. [http://dx.doi.org/10.1128/MCB.25.24.10895-10906.2005]. [PMID: 16314513].
[89]
Katoh Y, Itoh K, Yoshida E, Miyagishi M, Fukamizu A, Yamamoto M. Two domains of Nrf2 cooperatively bind CBP, a CREB binding protein, and synergistically activate transcription. Genes Cells 2001; 6(10): 857-68. [http://dx.doi.org/10.1046/j.1365-2443.2001.00469.x]. [PMID: 11683914].
[90]
Kim JH, Yu S, Chen JD, Kong AN. The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains. Oncogene 2013; 32(4): 514-27. [http://dx.doi.org/10.1038/onc.2012.59]. [PMID: 22370642].
[91]
Ahmed SMU, Luo L, Namani A, Wang XJ, Tang X. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 2017; 1863(2): 585-97. [http://dx.doi.org/10.1016/j.bbadis.2016.11.005]. [PMID: 27825853].
[92]
Komatsu M, Kurokawa H, Waguri S, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 2010; 12(3): 213-23. [http://dx.doi.org/10.1038/ncb2021]. [PMID: 20173742].
[93]
Chi X, Yao W, Xia H, et al. Elevation of HO-1 Expression Mitigates Intestinal Ischemia-Reperfusion Injury and Restores Tight Junction Function in a Rat Liver Transplantation Model. Oxid Med Cell Longev 2015; 2015986075 [http://dx.doi.org/10.1155/2015/986075]. [PMID: 26064429].
[94]
Steele ML, Fuller S, Patel M, Kersaitis C, Ooi L, Münch G. Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells. Redox Biol 2013; 1(1): 441-5. [http://dx.doi.org/10.1016/j.redox.2013.08.006]. [PMID: 24191238].
[95]
Qiu F, Chen YR, Liu X, et al. Arginine starvation impairs mitochondrial respiratory function in ASS1-deficient breast cancer cells. Sci Signal 2014; 7(319): ra31-1. [http://dx.doi.org/10.1126/scisignal.2004761]. [PMID: 24692592].
[96]
Abdelmagid SA, Rickard JA, McDonald WJ, Thomas LN, Too CK. CAT-1-mediated arginine uptake and regulation of nitric oxide synthases for the survival of human breast cancer cell lines. J Cell Biochem 2011; 112(4): 1084-92. [http://dx.doi.org/10.1002/jcb.23022]. [PMID: 21308737].
[97]
Riess C, Shokraie F, Classen CF, et al. Arginine-Depleting Enzymes - An Increasingly Recognized Treatment Strategy for Therapy-Refractory Malignancies. Cell Physiol Biochem 2018; 51(2): 854-70. [http://dx.doi.org/10.1159/000495382]. [PMID: 30466103].
[98]
Patil MD, Bhaumik J, Babykutty S, Banerjee UC, Fukumura D. Arginine dependence of tumor cells: targeting a chink in cancer’s armor. Oncogene 2016; 35(38): 4957-72. [http://dx.doi.org/10.1038/onc.2016.37]. [PMID: 27109103].
[99]
Singh R, Pervin S, Karimi A, Cederbaum S, Chaudhuri G. Arginase activity in human breast cancer cell lines: N(omega)-hydroxy-L-arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells. Cancer Res 2000; 60(12): 3305-12. [PMID: 10866325].
[100]
Fahs CA, Heffernan KS, Fernhall B. Hemodynamic and vascular response to resistance exercise with L-arginine. Med Sci Sports Exerc 2009; 41(4): 773-9. [http://dx.doi.org/10.1249/MSS.0b013e3181909d9d]. [PMID: 19276857].
[101]
Ferguson JE, Orlando RA. Curcumin reduces cytotoxicity of 5-Fluorouracil treatment in human breast cancer cells. J Med Food 2014; 18(4): 1-6. [http://dx.doi.org/10.1089/jmf.2013.0086]. [PMID: 24476216].
[102]
Ghiringhelli F, Apetoh L. Enhancing the anticancer effects of 5-fluorouracil: Current challenges and future perspectives. Biomed J 2015; 38(2): 111-6. [http://dx.doi.org/10.4103/2319-4170.130923]. [PMID: 25163503].
[103]
Traverso N, Ricciarelli R, Nitti M, et al. Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev 2013; 2013972913 [http://dx.doi.org/10.1155/2013/972913]. [PMID: 23766865].
[104]
Ravelli A, Roviello G, Cretella D, et al. Tumor-infiltrating lymphocytes and breast cancer: Beyond the prognostic and predictive utility. Tumour Biol 2017; 39(4)1010428317695023 [http://dx.doi.org/10.1177/1010428317695023]. [PMID: 28378631].

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