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2000
Volume 25, Issue 11
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

Lung cancer is a highly aggressive tumor with limited therapeutic options. The misregulation of Androgen Receptor (AR) signaling has been observed in lung cancer. Therefore, inhibiting AR signaling is a promising strategy for treating lung cancer.

Objective

Selective Androgen Receptor Modulators (SARMs) are small molecule drugs with a high affinity for the AR. S4, a member of SARMs was potentially positioned as a promising therapeutic agent in A549 lung cancer cells owing to its high bioavailability, lesser side effects, and novelty in cancer.

Methods

We employed several techniques to investigate the potential anti-carcinogenic effect of S4 on A549 cells at cellular level. The cytotoxicity of S4 was investigated thorough MTT, and the IC value was identified as 0.22 mM. Then, the anchorage-dependent and -independent colonization of cells were assessed by colony formation and soft agar assays, respectively. Additionally, migration capacity, apoptosis, proliferation, senescene, cell-cycle progression of cells was examined thoroughly. In addition, gene expression profile and metabolome signature were explored qRT-PCR and metabolomics, respectively to provide molecular links for S4 mode of action.

Results

Our findings demonstrate that S4 inhibited growth, migration, and proliferation while inducing apoptosis. S4 significantly upregulated the , and genes while downregulating , and expression. S4 treatment drastically altered the metabolome signature, and enrichment of cancer related pathways by altered metabolites was noteworthy.

Conclusion

We report the first study evaluating the potential anti-carcinogenic effects of S4 on lung cancer which would bridge the gap on the utility of SARMs as inhibitors of lung cancer. Our results suggest that S4 could be considered as a promising drug candidate to test further for lung cancer treatment.

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References

  1. TravisW.D. BrambillaE. NicholsonA.G. YatabeY. AustinJ.H.M. BeasleyM.B. ChirieacL.R. DacicS. DuhigE. FliederD.B. GeisingerK. HirschF.R. IshikawaY. KerrK.M. NoguchiM. PelosiG. PowellC.A. TsaoM.S. WistubaI. PanelW.H.O. The 2015 world health organization classification of lung tumors.J. Thorac. Oncol.20151091243126010.1097/JTO.0000000000000630 26291008
     [Google Scholar]
  2. SocinskiM.A. ObasajuC. GandaraD. HirschF.R. BonomiP. BunnP.A.Jr KimE.S. LangerC.J. NataleR.B. NovelloS. Paz-AresL. PérolM. ReckM. RamalingamS.S. ReynoldsC.H. SpigelD.R. WakeleeH. ThatcherN. Current and emergent therapy options for advanced squamous cell lung cancer.J. Thorac. Oncol.201813216518310.1016/j.jtho.2017.11.111 29175116
     [Google Scholar]
  3. DaveyR.A. GrossmannM. Androgen receptor structure, function and biology: From bench to bedside.Clin. Biochem. Rev.2016371315 27057074
     [Google Scholar]
  4. JinH-J. KimJ. YuJ. Androgen receptor genomic regulation.Transl. Androl. Urol.201323157177 25237629
     [Google Scholar]
  5. GaoW. DaltonJ.T. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs).Drug Discov. Today2007125-624124810.1016/j.drudis.2007.01.003 17331889
     [Google Scholar]
  6. GaoW. KearbeyJ.D. NairV.A. ChungK. ParlowA.F. MillerD.D. DaltonJ.T. Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia.Endocrinology2004145125420542810.1210/en.2004‑0627 15308613
     [Google Scholar]
  7. GaoW. ReiserP.J. CossC.C. PhelpsM.A. KearbeyJ.D. MillerD.D. DaltonJ.T. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats.Endocrinology2005146114887489710.1210/en.2005‑0572 16099859
     [Google Scholar]
  8. KawanamiT. TanakaT. HamaguchiY. NomiyamaT. NawataH. YanaseT. Selective androgen receptor modulator S42 suppresses prostate cancer cell proliferation.Endocrinology201815941774179210.1210/en.2018‑00099 29444261
     [Google Scholar]
  9. NyquistM.D. AngL.S. CorellaA. ColemanI.M. MeersM.P. ChristianiA.J. PierceC. JanssensD.H. MeadeH.E. BoseA. BradyL. HowardT. SarkarN.D. FrankS.B. DumpitR.F. DaltonJ.T. CoreyE. PlymateS.R. HaffnerM.C. MostaghelE.A. NelsonP.S. Selective androgen receptor modulators activate the canonical prostate cancer androgen receptor program and repress cancer growth.J. Clin. Invest.20212021131
     [Google Scholar]
  10. ChisamoreM.J. GentileM.A. DillonG.M. BaranM. GamboneC. RileyS. SchmidtA. FloresO. WilkinsonH. AlvesS.E. A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R–3327G and anabolic activity on skeletal muscle mass & function in castrated mice.J. Steroid Biochem. Mol. Biol.2016163889710.1016/j.jsbmb.2016.04.007 27106747
     [Google Scholar]
  11. SolomonZ.J. MirabalJ.R. MazurD.J. KohnT.P. LipshultzL.I. PastuszakA.W. Selective androgen receptor modulators: current knowledge and clinical applications.Sex. Med. Rev.201971849410.1016/j.sxmr.2018.09.006 30503797
     [Google Scholar]
  12. YavuzM. TakanlouL.S. AvcıÇ.B. DemircanT. A selective androgen receptor modulator, S4, displays robust anti-cancer activity on hepatocellular cancer cells by negatively regulating PI3K/AKT/mTOR signalling pathway.Gene202386914739010.1016/j.gene.2023.147390 36990257
     [Google Scholar]
  13. BölükA. YavuzM. TakanlouM.S. AvcıÇ.B. DemircanT. In vitro anti-carcinogenic effect of andarine as a selective androgen receptor modulator on MIA-PaCa2 cells by decreased proliferation and cell-cycle arrest at G0/G1 phase.Biochem. Biophys. Res. Commun.202367113213910.1016/j.bbrc.2023.06.016 37302286
     [Google Scholar]
  14. ChangC. LeeS.O. YehS. ChangT.M. Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver.Oncogene201433253225323410.1038/onc.2013.274 23873027
     [Google Scholar]
  15. MikkonenL. PihlajamaaP. SahuB. ZhangF.P. JänneO.A. Androgen receptor and androgen-dependent gene expression in lung.Mol. Cell. Endocrinol.20103171-2142410.1016/j.mce.2009.12.022 20035825
     [Google Scholar]
  16. RecchiaA.G. MustiA.M. LanzinoM. PannoM.L. TuranoE. ZumpanoR. BelfioreA. AndòS. MaggioliniM. A cross-talk between the androgen receptor and the epidermal growth factor receptor leads to p38MAPK-dependent activation of mTOR and cyclinD1 expression in prostate and lung cancer cells.Int. J. Biochem. Cell Biol.200941360361410.1016/j.biocel.2008.07.004 18692155
     [Google Scholar]
  17. GockelL.M. PfeiferV. BaltesF. BachmaierR.D. WagnerK.G. BendasG. GütschowM. SosičI. SteinebachC. Design, synthesis, and characterization of PROTACs targeting the androgen receptor in prostate and lung cancer models.Arch. Pharm. (Weinheim)20223555210046710.1002/ardp.202100467 35128717
     [Google Scholar]
  18. NazhaB. ZhangC. ChenZ. RaginC. OwonikokoT.K. Concurrent androgen deprivation therapy for prostate cancer improves survival for synchronous or metachronous non-small cell lung cancer: A SEER–medicare database analysis.Cancers (Basel)20221413320610.3390/cancers14133206 35804979
     [Google Scholar]
  19. YavuzM. DemircanT. Hydroquinidine demonstrates remarkable antineoplastic effects on non-small cell lung cancer cells.Curr. Mol. Med.202424911591168 37592773
     [Google Scholar]
  20. ChuC.J. WuG.S. MaH.I. VenkatesanP. ThirumalaivasanN. WuS.P. A fluorescent turn-on probe for detection of hypochlorus acid and its bioimaging in living cells.Spectrochim. Acta A Mol. Biomol. Spectrosc.202023311823410.1016/j.saa.2020.118234 32163873
     [Google Scholar]
  21. WeiL.F. ChenC.Y. LaiC.K. ThirumalaivasanN. WuS.P. A nano-molar fluorescent turn-on probe for copper(II) detection in living cells.Methods2019168182310.1016/j.ymeth.2019.04.023 31055073
     [Google Scholar]
  22. ThirumalaivasanN. VenkatesanP. WuS.P. Highly selective turn-on probe for H 2 S with imaging applications in vitro and in vivo.New J. Chem.20174122135101351510.1039/C7NJ02869E
     [Google Scholar]
  23. PangZ. LuY. ZhouG. HuiF. XuL. ViauC. SpigelmanA.F. MacDonaldP.E. WishartD.S. LiS. XiaJ. MetaboAnalyst 6.0: towards a unified platform for metabolomics data processing, analysis and interpretation.Nucleic Acids Res.202452W1W398W40610.1093/nar/gkae253 38587201
     [Google Scholar]
  24. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global Cancer Statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  25. MorgenszternD. NgS.H. GaoF. GovindanR. Trends in stage distribution for patients with non-small cell lung cancer: A National Cancer Database survey.J. Thorac. Oncol.201051293310.1097/JTO.0b013e3181c5920c 19952801
     [Google Scholar]
  26. EttingerD.S. WoodD.E. AisnerD.L. AkerleyW. BaumanJ.R. BharatA. BrunoD.S. ChangJ.Y. ChirieacL.R. D’AmicoT.A. DillingT.J. DowellJ. GettingerS. GubensM.A. HegdeA. HennonM. LacknerR.P. LanutiM. LealT.A. LinJ. LooB.W.Jr LovlyC.M. MartinsR.G. MassarelliE. MorgenszternD. NgT. OttersonG.A. PatelS.P. RielyG.J. SchildS.E. ShapiroT.A. SinghA.P. StevensonJ. TamA. YanagawaJ. YangS.C. GregoryK.M. HughesM. NCCN guidelines insights: Non–small cell lung cancer, version 2.2021.J. Natl. Compr. Canc. Netw.202119325426610.6004/jnccn.2021.0013 33668021
     [Google Scholar]
  27. HerbstR.S. MorgenszternD. BoshoffC. The biology and management of non-small cell lung cancer.Nature2018553768944645410.1038/nature25183 29364287
     [Google Scholar]
  28. DuanJ. CuiL. ZhaoX. BaiH. CaiS. WangG. ZhaoZ. ZhaoJ. ChenS. SongJ. QiC. WangQ. HuangM. ZhangY. HuangD. BaiY. SunF. LeeJ.J. WangZ. WangJ. Use of immunotherapy with programmed cell death 1 vs programmed cell death ligand 1 inhibitors in patients with cancer.JAMA Oncol.20206337538410.1001/jamaoncol.2019.5367 31876895
     [Google Scholar]
  29. XiaL. LiuY. WangY. PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: Current status and future directions.Oncologist201924S1S31S4110.1634/theoncologist.2019‑IO‑S1‑s05 30819829
     [Google Scholar]
  30. BethuneG. BethuneD. RidgwayN. XuZ. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update.J. Thorac. Dis.2010214851 22263017
     [Google Scholar]
  31. RoskoskiR. Jr Anaplastic lymphoma kinase (ALK) inhibitors in the treatment of ALK-driven lung cancers.Pharmacol. Res.201711734335610.1016/j.phrs.2017.01.007 28077299
     [Google Scholar]
  32. HuangL. FuL. Mechanisms of resistance to EGFR tyrosine kinase inhibitors.Acta Pharm. Sin. B20155539040110.1016/j.apsb.2015.07.001 26579470
     [Google Scholar]
  33. LimZ.F. MaP.C. Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy.J. Hematol. Oncol.201912113410.1186/s13045‑019‑0818‑2 31815659
     [Google Scholar]
  34. LiuW. DuY. WenR. YangM. XuJ. Drug resistance to targeted therapeutic strategies in non-small cell lung cancer.Pharmacol. Ther.202020610743810.1016/j.pharmthera.2019.107438 31715289
     [Google Scholar]
  35. YehS.D. YangP.C. LuH.H. ChangC. WuC.W. Targeting androgen receptor as a new potential therapeutic approach to battle tobacco carcinogens-induced non-small cell lung cancer.J. Transl. Med.201210S2A810.1186/1479‑5876‑10‑S2‑A8
     [Google Scholar]
  36. LuH.H. YehS.D. ChouY.T. TsaiY.T. ChangC. WuC.W. Abstract 2126: Androgen receptor regulates lung cancer progress through modulation of OCT-4 expression.Cancer Res.2011718Suppl.212610.1158/1538‑7445.AM2011‑2126
     [Google Scholar]
  37. NoronhaC. RibeiroA.S. TaipaR. CastroD.S. ReisJ. FariaC. ParedesJ. Cadherin expression and EMT: A focus on gliomas.Biomedicines2021910132810.3390/biomedicines9101328 34680444
     [Google Scholar]
  38. DouM. ZhuK. FanZ. ZhangY. ChenX. ZhouX. DingX. LiL. GuZ. GuoM. YanM. DengX. ShenP. WangS. Reproductive hormones and their receptors may affect lung cancer.Cell. Physiol. Biochem.20174441425143410.1159/000485538 29186712
     [Google Scholar]
  39. MaasbergM. RotschM. JaquesG. Enderle-SchmidtU. WeehleR. HavemannK. Androgen receptors, androgen-dependent proliferation, and 5α-reductase activity of small-cell lung cancer cell lines.Int. J. Cancer198943468569110.1002/ijc.2910430424 2539332
     [Google Scholar]
  40. LinP. ChangJ.T. KoJ.L. LiaoS.H. LoW.S. Reduction of androgen receptor expression by benzo[a]pyrene and 7,8-dihydro-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in human lung cells.Biochem. Pharmacol.20046781523153010.1016/j.bcp.2003.12.018 15041469
     [Google Scholar]
  41. ZhangH. LiX.X. YangY. ZhangY. WangH.Y. ZhengX.F.S. Significance and mechanism of androgen receptor overexpression and androgen receptor/mechanistic target of rapamycin cross-talk in hepatocellular carcinoma.Hepatology20186762271228610.1002/hep.29715 29220539
     [Google Scholar]
  42. KawaharaT. InoueS. KashiwagiE. ChenJ. IdeH. MizushimaT. LiY. ZhengY. MiyamotoH. Enzalutamide as an androgen receptor inhibitor prevents urothelial tumorigenesis.Am. J. Cancer Res.201771020412050 29119053
     [Google Scholar]
  43. LiP. ChenJ. MiyamotoH. Androgen receptor signaling in bladder cancer.Cancers (Basel)2017922010.3390/cancers9020020 28241422
     [Google Scholar]
  44. BartonV.N. D’AmatoN.C. GordonM.A. LindH.T. SpoelstraN.S. BabbsB.L. HeinzR.E. EliasA. JedlickaP. JacobsenB.M. RicherJ.K. Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo.Mol. Cancer Ther.201514376977810.1158/1535‑7163.MCT‑14‑0926 25713333
     [Google Scholar]
  45. GiovannelliP. Di DonatoM. AuricchioF. CastoriaG. MigliaccioA. Androgens induce invasiveness of triple negative breast cancer cells through AR/Src/PI3-K complex assembly.Sci. Rep.201991449010.1038/s41598‑019‑41016‑4 30872694
     [Google Scholar]
  46. NarayananR. AhnS. CheneyM.D. YepuruM. MillerD.D. SteinerM.S. DaltonJ.T. Selective androgen receptor modulators (SARMs) negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.PLoS One201497e10320210.1371/journal.pone.0103202 25072326
     [Google Scholar]
  47. BalkS.P. KnudsenK.E. AR the cell cycle, and prostate cancer.Nucl. Recept. Signal.200861nrs.0600110.1621/nrs.06001 18301781
     [Google Scholar]
  48. SheachL.A. AdeneyE.M. KucukmetinA. WilkinsonS.J. FisherA.D. ElattarA. RobsonC.N. EdmondsonR.J. Androgen-related expression of G-proteins in ovarian cancer.Br. J. Cancer2009101349850310.1038/sj.bjc.6605153 19623182
     [Google Scholar]
  49. ZaidiM.R. LiebermannD.A. Gadd45 in Senescence.Adv. Exp. Med. Biol.2022136010911610.1007/978‑3‑030‑94804‑7_8 35505166
     [Google Scholar]
  50. KallenbachJ. Atri RoozbahaniG. Heidari HorestaniM. BaniahmadA. Distinct mechanisms mediating therapy-induced cellular senescence in prostate cancer.Cell Biosci.202212120010.1186/s13578‑022‑00941‑0 36522745
     [Google Scholar]
  51. HessenkemperW. RoedigerJ. BartschS. HoutsmullerA.B. van RoyenM.E. PetersenI. GrimmM.O. BaniahmadA. A natural androgen receptor antagonist induces cellular senescence in prostate cancer cells.Mol. Endocrinol.201428111831184010.1210/me.2014‑1170 25203674
     [Google Scholar]
  52. CarpenterV. SalehT. Min LeeS. MurrayG. ReedJ. SouersA. FaberA.C. HaradaH. Gewirtz D.A. Androgen-deprivation induced senescence in prostate cancer cells is permissive for the development of castration-resistance but susceptible to senolytic therapy.Biochem. Pharmacol.202119311476510.1016/j.bcp.2021.114765 34536356
     [Google Scholar]
  53. HartatiF.K. KurniaD. NafisahW. HaryantoI.B. Potential anticancer agents of curcuma aeruginosa-based kombucha: In vitro and in silico study.Food Chem. Adv.20244100606
     [Google Scholar]
  54. HayakawaS. OhishiT. MiyoshiN. OishiY. NakamuraY. IsemuraM. Anti-cancer effects of green tea epigallocatchin-3-gallate and coffee chlorogenic acid.Molecules20202519455310.3390/molecules25194553 33027981
     [Google Scholar]
  55. WangQ. GaoP. WangX. DuanY. The early diagnosis and monitoring of squamous cell carcinoma via saliva metabolomics.Sci. Rep.201441680210.1038/srep06802 25354816
     [Google Scholar]
  56. ŁuczykowskiK. WarmuzińskaN. OperaczS. StryjakI. BogusiewiczJ. JacynaJ. WawrzyniakR. Struck-LewickaW. MarkuszewskiM.J. BojkoB. Metabolic evaluation of urine from patients diagnosed with high grade (HG) bladder cancer by SPME-LC-MS method.Molecules2021268219410.3390/molecules26082194 33920347
     [Google Scholar]
  57. BagheriP. HoangK. FungA.A. HussainS. ShiL. Visualizing cancer cell metabolic dynamics regulated with aromatic amino acids using DO-SRS and 2PEF microscopy.Front. Mol. Biosci.2021877970210.3389/fmolb.2021.779702 34977157
     [Google Scholar]
  58. ZurloG. LiuX. TakadaM. FanC. SimonJ.M. PtacekT.S. RodriguezJ. von KriegsheimA. LiuJ. LocasaleJ.W. RobinsonA. ZhangJ. HollerJ.M. KimB. ZikánováM. BierauJ. XieL. ChenX. LiM. PerouC.M. ZhangQ. Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer.Nat. Commun.2019101517710.1038/s41467‑019‑13168‑4 31729379
     [Google Scholar]
  59. Taha-MehlitzS. BiancoG. Coto-LlerenaM. KancherlaV. BantugG.R. GallonJ. ErcanC. PanebiancoF. Eppenberger-CastoriS. von StraussM. StaubliS. BolliM. PeterliR. MatterM.S. TerraccianoL.M. von FlüeM. NgC.K.Y. SoysalS.D. KollmarO. PiscuoglioS. Adenylosuccinate lyase is oncogenic in colorectal cancer by causing mitochondrial dysfunction and independent activation of NRF2 and mTOR-MYC-axis.Theranostics20211194011402910.7150/thno.50051 33754045
     [Google Scholar]
  60. LiaoJ. SongQ. LiJ. DuK. ChenY. ZouC. MoZ. Carcinogenic effect of adenylosuccinate lyase (ADSL) in prostate cancer development and progression through the cell cycle pathway.Cancer Cell Int.202121146710.1186/s12935‑021‑02174‑6 34488772
     [Google Scholar]
  61. OzawaM. HondaK. NakaiI. KishidaA. OhsakiA. Hypaphorine, an indole alkaloid from Erythrina velutina, induced sleep on normal mice.Bioorg. Med. Chem. Lett.200818143992399410.1016/j.bmcl.2008.06.002 18571406
     [Google Scholar]
  62. LuanG. TieF. YuanZ. LiG. HeJ. WangZ. WangH. Hypaphorine, an indole alkaloid isolated from Caragana korshinskii KOM., inhibites 3T3-L1 adipocyte differentiation and improves insulin sensitivity in vitro.Chem. Biodivers.2017147e170003810.1002/cbdv.201700038 28398659
     [Google Scholar]
  63. WeiC. ZhouW. Hypaphorine ameliorates lipid accumulation and inflammation in a cellular model of non alcoholic fatty liver by regulating p38/JNK and NF κB signaling pathways.Trop. J. Pharm. Res.202321122569257410.4314/tjpr.v21i12.10
     [Google Scholar]
  64. Ranea-RoblesP. HoutenS.M. The biochemistry and physiology of long-chain dicarboxylic acid metabolism.Biochem. J.2023480960762710.1042/BCJ20230041 37140888
     [Google Scholar]
  65. IsmailI.T. FiehnO. ElfertA. HelalM. SalamaI. El-SaidH. Sugar alcohols have a key role in pathogenesis of chronic liver disease and hepatocellular carcinoma in whole blood and liver tissues.Cancers (Basel)202012248410.3390/cancers12020484 32092943
     [Google Scholar]
  66. TammaliR. SrivastavaS.K. RamanaK.V. Targeting aldose reductase for the treatment of cancer.Curr. Cancer Drug Targets201111556057110.2174/156800911795655958 21486217
     [Google Scholar]
  67. SyamprasadN.P. JainS. RajdevB. PrasadN. KallipalliR. NaiduV.G.M. Aldose reductase and cancer metabolism: The master regulator in the limelight.Biochem. Pharmacol.202321111552810.1016/j.bcp.2023.115528 37011733
     [Google Scholar]
  68. AmelioI. CutruzzoláF. AntonovA. AgostiniM. MelinoG. Serine and glycine metabolism in cancer.Trends Biochem. Sci.201439419119810.1016/j.tibs.2014.02.004 24657017
     [Google Scholar]
  69. ShuvalovO. PetukhovA. DaksA. FedorovaO. VasilevaE. BarlevN.A. One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy.Oncotarget2017814239552397710.18632/oncotarget.15053 28177894
     [Google Scholar]
  70. Sánchez-CastilloA. HeylenE. HounjetJ. SavelkoulsK.G. LieuwesN.G. BiemansR. DuboisL.J. ReyndersK. RouschopK.M. VaesR.D.W. De KeersmaeckerK. LambrechtM. HendriksL.E.L. De RuysscherD.K.M. VooijsM. KampenK.R. Targeting serine/glycine metabolism improves radiotherapy response in non-small cell lung cancer.Br. J. Cancer2024130456858410.1038/s41416‑023‑02553‑y 38160212
     [Google Scholar]
  71. BonifácioV.D.B. PereiraS.A. SerpaJ. VicenteJ.B. Cysteine metabolic circuitries: Druggable targets in cancer.Br. J. Cancer2021124586287910.1038/s41416‑020‑01156‑1 33223534
     [Google Scholar]
  72. DesideriE. CiccaroneF. CirioloM.R. Targeting glutathione metabolism: Partner in crime in anticancer therapy.Nutrients2019118192610.3390/nu11081926 31426306
     [Google Scholar]
  73. Georgiou-SiafisS.K. TsiftsoglouA.S. The key role of GSH in keeping the redox balance in mammalian cells: Mechanisms and significance of GSH in detoxification via formation of conjugates.Antioxidants20231211195310.3390/antiox12111953 38001806
     [Google Scholar]
  74. KennedyL. SandhuJ.K. HarperM.E. Cuperlovic-CulfM. Role of glutathione in cancer: From mechanisms to therapies.Biomolecules20201010142910.3390/biom10101429 33050144
     [Google Scholar]
  75. ZhangN. Role of methionine on epigenetic modification of DNA methylation and gene expression in animals.Anim. Nutr.201841111610.1016/j.aninu.2017.08.009 30167479
     [Google Scholar]
  76. LiX. ZhangH.S. Amino acid metabolism, redox balance and epigenetic regulation in cancer.FEBS J.2024291341242910.1111/febs.16803 37129434
     [Google Scholar]
  77. JungM.K. OkekunleA.P. LeeJ.E. SungM.K. LimY.J. Role of branched-chain amino acid metabolism in tumor development and progression.J. Cancer Prev.202126423724310.15430/JCP.2021.26.4.237 35047449
     [Google Scholar]
  78. XuE. JiB. JinK. ChenY. Branched-chain amino acids catabolism and cancer progression: focus on therapeutic interventions.Front. Oncol.202313122063810.3389/fonc.2023.1220638 37637065
     [Google Scholar]
  79. MikalayevaV. PankevičiūtėM. ŽvikasV. SkeberdisV.A. BordelS. Contribution of branched chain amino acids to energy production and mevalonate synthesis in cancer cells.Biochem. Biophys. Res. Commun.2021585616710.1016/j.bbrc.2021.11.034 34794035
     [Google Scholar]
  80. ZhangS. ZengX. RenM. MaoX. QiaoS. Novel metabolic and physiological functions of branched chain amino acids: A review.J. Anim. Sci. Biotechnol.2017811010.1186/s40104‑016‑0139‑z 28127425
     [Google Scholar]
  81. PengH. WangY. LuoW. Multifaceted role of branched-chain amino acid metabolism in cancer.Oncogene202039446747675610.1038/s41388‑020‑01480‑z 32978521
     [Google Scholar]
  82. TongB. BarbulA. Cellular and physiological effects of arginine.Mini Rev. Med. Chem.20044882383210.2174/1389557043403305 15544543
     [Google Scholar]
  83. PatilM.D. BhaumikJ. BabykuttyS. BanerjeeU.C. FukumuraD. Arginine dependence of tumor cells: targeting a chink in cancer’s armor.Oncogene201635384957497210.1038/onc.2016.37 27109103
     [Google Scholar]
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Unveiling the Potential of S4 on Non-small Cell Lung Cancer Cells: Impact on Proliferation, Apoptosis, Senescence, and Metabolome Profile
Anti-Cancer Agents in Medicinal Chemistry 25, 785 (2025); https://doi.org/10.2174/0118715206350735241224073200
/content/journals/acamc/10.2174/0118715206350735241224073200
/content/journals/acamc/10.2174/0118715206350735241224073200
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  • Article Type:     Research Article
Keyword(s): androgen receptor signaling; anti-cancer agent; anti-carcinogenic effects; lung cancer; S4; Selective androgen receptor modulator

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