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2000
Volume 21, Issue 1
  • ISSN: 2772-4328
  • E-ISSN: 2772-4336

Abstract

Introduction

Experimental evidence has demonstrated that compounds of natural origin possess adjuvant anti-cancer properties, and their combination with anti-cancer drugs has the potential to reduce drug resistance in cancer treatment exhibiting chemoprotective effects.

Methods

Fisetin (FIS), a flavonoid-structured polyphenolic compound found in various vegetables and fruits, is used as a yellow/ochre coloring agent and shows diverse pharmacological and biological effects. FIS can modulate various signaling pathways in relation to oxidative stress, inflammation, cell proliferation, metastasis, and angiogenesis. Thus, FIS is proposed to be a beneficial agent for preventing and treating numerous human malignancies. Awareness of natural compound action mechanisms paves the way for scientific communities, healthcare organizations, and the pharmaceutical industry to develop and introduce new drugs to treat diseases. In this paper, the general properties of FIS were highlighted first, and later, using the Scopus database, all related scientific literature regarding the studies that investigated the effects of FIS on lung cancer was collected.

Results

The critical points were extracted from the research works, and possible effects and molecular mechanisms of FIS on cancer cells were reviewed, and a comprehensive discussion about the roles of this phytochemical on different signaling pathways that were very crucial in lung cancer cells was provided.

Conclusion

Finally, the current challenges and future perspectives of lung cancer prevention and therapy approaches using FIS were addressed.

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2025-04-04
2026-03-10
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References

  1. SaadonyE.M.T. ZabermawiN.M. ZabermawiN.M. Nutritional aspects and health benefits of bioactive plant compounds against infectious diseases: A review.Food Rev. Int.20211123
    [Google Scholar]
  2. BraicuC. ZanoagaO. ZimtaA-A. Natural compounds modulate the crosstalk between apoptosis-and autophagy-regulated signaling pathways: Controlling the uncontrolled expansion of tumor cells. Elsevier:Seminars In cancer Biology.202080218236
    [Google Scholar]
  3. ChanvorachoteP. ChamniS. NinsontiaC. PhiboonchaiyananP.P. Potential anti-metastasis natural compounds for lung cancer.Anticancer Res.201636115707571810.21873/anticanres.11154 27793892
    [Google Scholar]
  4. SüntarI. Importance of ethnopharmacological studies in drug discovery: Role of medicinal plants.Phytochem. Rev.20201951199120910.1007/s11101‑019‑09629‑9
    [Google Scholar]
  5. OgutE. ArmaganK. GülZ. The role of syringic acid as a neuroprotective agent for neurodegenerative disorders and future expectations.Metab. Brain Dis.202237485988010.1007/s11011‑022‑00960‑3 35334041
    [Google Scholar]
  6. PandeyK.B. RizviS.I. Plant polyphenols as dietary antioxidants in human health and disease.Oxid. Med. Cell. Longev.20092527027810.4161/oxim.2.5.9498 20716914
    [Google Scholar]
  7. GüzeladÖ. ÖzkanA. ParlakH. Protective mechanism of Syringic acid in an experimental model of Parkinson’s disease.Metab. Brain Dis.20213651003101410.1007/s11011‑021‑00704‑9 33666819
    [Google Scholar]
  8. OgutE. AkcayG. YildirimF.B. DerinN. AslanM. The influence of syringic acid treatment on total dopamine levels of the hippocampus and on cognitive behavioral skills.Int. J. Neurosci.2022132990190910.1080/00207454.2020.1849191 33175581
    [Google Scholar]
  9. PalHC PearlmanRL AfaqF Fisetin and its role in chronic diseases.Springer: Anti-inflammatory Nutraceuticals and Chronic Diseases20162134410.1007/978‑3‑319‑41334‑1_10
    [Google Scholar]
  10. ZhanG. PanL. TuK. JiaoS. Antitumor, antioxidant, and nitrite scavenging effects of Chinese water chestnut (Eleocharis dulcis) peel flavonoids.J. Food Sci.20168110H2578H258610.1111/1750‑3841.13434 27603811
    [Google Scholar]
  11. RogerL. TomasF. GireV. Mechanisms and regulation of cellular senescence.Int. J. Mol. Sci.202122231317310.3390/ijms222313173 34884978
    [Google Scholar]
  12. KuilmanT. MichaloglouC. MooiW.J. PeeperD.S. The essence of senescence: Figure 1.Genes Dev.201024222463247910.1101/gad.1971610 21078816
    [Google Scholar]
  13. CalcinottoA. KohliJ. ZagatoE. PellegriniL. DemariaM. AlimontiA. Cellular senescence: Aging, cancer, and injury.Physiol. Rev.20199921047107810.1152/physrev.00020.2018 30648461
    [Google Scholar]
  14. MaherP. Fisetin acts on multiple pathways to reduce the impact of age and disease on CNS function.Front. Biosci. (Schol. Ed.)201575810.2741/s425 25961687
    [Google Scholar]
  15. YousefzadehM.J. ZhuY. McGowanS.J. Fisetin is a senotherapeutic that extends health and lifespan.EBioMedicine201836182810.1016/j.ebiom.2018.09.015 30279143
    [Google Scholar]
  16. ParkS. KimB.K. ParkS.K. Effects of fisetin, a plant-derived flavonoid, on response to oxidative stress, aging, and age-related diseases in Caenorhabditis elegans.Pharmaceuticals20221512152810.3390/ph15121528 36558979
    [Google Scholar]
  17. HuardC.A. GaoX. HazraD.M.E. Effects of Fisetin treatment on cellular senescence of various tissues and organs of old sheep.Antioxidants2023128164610.3390/antiox12081646 37627641
    [Google Scholar]
  18. ZhangL. TongX. HuangJ. Fisetin alleviated bleomycin-induced pulmonary fibrosis partly by rescuing alveolar epithelial cells from senescence.Front. Pharmacol.20201155369010.3389/fphar.2020.553690 33381023
    [Google Scholar]
  19. LallR.K. AdhamiV.M. MukhtarH. Dietary flavonoid fisetin for cancer prevention and treatment.Mol. Nutr. Food Res.20166061396140510.1002/mnfr.201600025 27059089
    [Google Scholar]
  20. ZhouC. HuangY. NieS. ZhouS. GaoX. ChenG. Biological effects and mechanisms of fisetin in cancer: A promising anti-cancer agent.Eur. J. Med. Res.202328129710.1186/s40001‑023‑01271‑8 37626424
    [Google Scholar]
  21. SimH. ChooS. KimJ. BaekM.C. BaeJ.S. Fisetin suppresses pulmonary inflammatory responses through heme oxygenase-1 mediated downregulation of inducible nitric oxide synthase.J. Med. Food202023111163116810.1089/jmf.2020.4755 33052744
    [Google Scholar]
  22. WuS.J. HuangW.C. ChengC.Y. WangM.C. ChengS.C. LiouC.J. Fisetin suppresses the inflammatory response and oxidative stress in bronchial epithelial cells.Nutrients2022149184110.3390/nu14091841 35565807
    [Google Scholar]
  23. AgravalH. SharmaJ.R. PrakashN. YadavU.C.S. Fisetin suppresses cigarette smoke extract-induced epithelial to mesenchymal transition of airway epithelial cells through regulating COX-2/MMPs/β-catenin pathway.Chem. Biol. Interact.202235110977110.1016/j.cbi.2021.109771 34864006
    [Google Scholar]
  24. AnsóE. ZuazoA. IrigoyenM. UrdaciM.C. RouzautA. IrujoM.J.J. Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism.Biochem. Pharmacol.201079111600160910.1016/j.bcp.2010.02.004 20153296
    [Google Scholar]
  25. RavichandranN. SureshG. RameshB. SivaV.G. Fisetin, a novel flavonol attenuates benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice.Food Chem. Toxicol.20114951141114710.1016/j.fct.2011.02.005 21315788
    [Google Scholar]
  26. WangJ. HuangS. Fisetin inhibits the growth and migration in the A549 human lung cancer cell line via the ERK1/2 pathway.Exp. Ther. Med.201815326672673 29467859
    [Google Scholar]
  27. MemarianiZ. AbbasS.Q. HassanuSS. AhmadiA. ChabraA. Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review.Pharmacol. Res.202117110526410.1016/j.phrs.2020.105264 33166734
    [Google Scholar]
  28. KhanN. SyedD.N. AhmadN. MukhtarH. Fisetin: A dietary antioxidant for health promotion.Antioxid. Redox Signal.201319215116210.1089/ars.2012.4901 23121441
    [Google Scholar]
  29. AntikaL.D. DewiR.M. Pharmacological aspects of fisetin.Asian Pac. J. Trop. Biomed.20211111910.4103/2221‑1691.300726
    [Google Scholar]
  30. KashyapD. SharmaA. SakK. TuliH.S. ButtarH.S. BishayeeA. Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy.Life Sci.2018194758710.1016/j.lfs.2017.12.005 29225112
    [Google Scholar]
  31. GrynkiewiczG. DemchukO.M. New perspectives for fisetin.Front Chem.2019769710.3389/fchem.2019.00697 31750288
    [Google Scholar]
  32. HuangM.C. HsuehT.Y. ChengY.Y. LinL.C. TsaiT.H. Pharmacokinetics and biliary excretion of fisetin in rats.J. Agric. Food Chem.201866256300630710.1021/acs.jafc.8b00917 29862816
    [Google Scholar]
  33. TouilY.S. AuzeilN. BoulinguezF. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite.Biochem. Pharmacol.201182111731173910.1016/j.bcp.2011.07.097 21840301
    [Google Scholar]
  34. SowaM. ŚlepokuraK. JonM.E. Improving solubility of fisetin by cocrystallization.CrystEngComm20141646105921060110.1039/C4CE01713G
    [Google Scholar]
  35. SowaM. ŚlepokuraK. JonM.E. Cocrystals of fisetin, luteolin and genistein with pyridinecarboxamide coformers: Crystal structures, analysis of intermolecular interactions, spectral and thermal characterization.CrystEngComm201315387696770810.1039/c3ce41285g
    [Google Scholar]
  36. ZhongR. FaragM.A. ChenM. HeC. XiaoJ. Recent advances in the biosynthesis, structure–activity relationships, formulations, pharmacology, and clinical trials of fisetin.eFood202231-2e310.1002/efd2.3
    [Google Scholar]
  37. SenguptaB. BanerjeeA. SenguptaP.K. Investigations on the binding and antioxidant properties of the plant flavonoid fisetin in model biomembranes.FEBS Lett.20045701-3778110.1016/j.febslet.2004.06.027 15251443
    [Google Scholar]
  38. RahmaniA.H. AlmatroudiA. AllemailemK.S. KhanA.A. AlmatroodiS.A. The potential role of fisetin, a flavonoid in cancer prevention and treatment.Molecules20222724900910.3390/molecules27249009 36558146
    [Google Scholar]
  39. GantiA.K. KleinA.B. CotarlaI. SealB. ChouE. Update of incidence, prevalence, survival, and initial treatment in patients with non–small cell lung cancer in the US.JAMA Oncol.20217121824183210.1001/jamaoncol.2021.4932 34673888
    [Google Scholar]
  40. HowladerN. ForjazG. MooradianM.J. The effect of advances in lung-cancer treatment on population mortality.N. Engl. J. Med.2020383764064910.1056/NEJMoa1916623 32786189
    [Google Scholar]
  41. J.FME RL SiegelM. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.2024713209249
    [Google Scholar]
  42. SungH. FerlayJ. SiegelR.L. 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]
  43. BartaJ.A. PowellC.A. WisniveskyJ.P. Global epidemiology of lung cancer.Ann. Glob. Health2019851810.5334/aogh.2419 30741509
    [Google Scholar]
  44. SharmaP. MehtaM. DhanjalD.S. Emerging trends in the novel drug delivery approaches for the treatment of lung cancer.Chem. Biol. Interact.201930910872010.1016/j.cbi.2019.06.033 31226287
    [Google Scholar]
  45. LakshmiS.P. ReddyA.T. BannoA. ReddyR.C. PPAR agonists for the prevention and treatment of lung cancer.PPAR Res.201720171810.1155/2017/8252796 28316613
    [Google Scholar]
  46. RavichandranN. SureshG. RameshB. ManikandanR. ChoiY.W. SivaV.G. Fisetin modulates mitochondrial enzymes and apoptotic signals in benzo(a)pyrene-induced lung cancer.Mol. Cell. Biochem.20143901-222523410.1007/s11010‑014‑1973‑y 24496750
    [Google Scholar]
  47. KangK.A. PiaoM.J. HyunJ.W. Fisetin induces apoptosis in human nonsmall lung cancer cells via a mitochondria-mediated pathway. In Vitro Cell. Dev. Biol. Anim.201551330030910.1007/s11626‑014‑9830‑6 25381036
    [Google Scholar]
  48. KangK.A. PiaoM.J. HewageM.S.R.K. Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway.Tumour Biol.20163779615962410.1007/s13277‑016‑4864‑x 26797785
    [Google Scholar]
  49. KimJ. LeeH. ParkJ. SimD. LeeH. Involvement of exportin 1 mediated c-myc and cullin 4A signaling in apoptotic effect of fisetin in non-small cell lung cancer cells.J. Oncol. Res. Ther.2023810169
    [Google Scholar]
  50. TabasumS. SinghR.P. Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition.Chem. Biol. Interact.2019303142110.1016/j.cbi.2019.02.020 30802432
    [Google Scholar]
  51. KhanN. AfaqF. KhusroF.H. AdhamiV.M. SuhY. MukhtarH. Dual inhibition of PI3K/AKT and mTOR signaling in human non-small cell lung cancer cells by a dietary flavonoid fisetin, International Journal of Cancer.J Intern du Cancer20121307169510.1002/ijc.26178 21618507
    [Google Scholar]
  52. EguchiH. KimuraR. MatsunagaH. Increase in anticancer drug-induced toxicity by fisetin in lung adenocarcinoma a549 spheroid cells mediated by the reduction of claudin-2 expression.Int. J. Mol. Sci.20222314753610.3390/ijms23147536 35886884
    [Google Scholar]
  53. LiaoY.C. ShihY.W. ChaoC.H. LeeX.Y. ChiangT.A. Involvement of the ERK signaling pathway in fisetin reduces invasion and migration in the human lung cancer cell line A549.J. Agric. Food Chem.200957198933894110.1021/jf902630w 19725538
    [Google Scholar]
  54. ZhuoW. ZhangL. ZhuY. ZhuB. ChenZ. Fisetin, a dietary bioflavonoid, reverses acquired Cisplatin-resistance of lung adenocarcinoma cells through MAPK/Survivin/Caspase pathway.Am. J. Transl. Res.201571020452052 26692948
    [Google Scholar]
  55. ZhangL. HuangY. ZhuoW. ZhuY. ZhuB. ChenZ. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.Am. J. Transl. Res.201681148574868 27904686
    [Google Scholar]
  56. Correia da SilvaD. ValentãoP. PereiraD.M. A survey of naturally occurring molecules as new endoplasmic reticulum stress activators with selective anticancer activity.Cancers202215129310.3390/cancers15010293 36612288
    [Google Scholar]
  57. RagelleH. MancietC.S. SeguinJ. Nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice.Int. J. Pharm.2012427245245910.1016/j.ijpharm.2012.02.025 22387278
    [Google Scholar]
  58. LingJ. WangY. MaL. ChangA. MengL. ZhangL. Exploration of potential targets and mechanisms of fisetin in the treatment of non‐small‐cell lung carcinoma via network pharmacology and in vitro validation.Evid. Based Complement. Alternat. Med.2022202211910.1155/2022/2383527 35733630
    [Google Scholar]
  59. ShiB. WangL.F. MengW.S. ChenL. MengZ.L. Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.Int. J. Oncol.20175062123213510.3892/ijo.2017.3970 28440400
    [Google Scholar]
  60. Klimaszewska-WiśniewskaA. Hałas-WiśniewskaM. GrzankaA. GrzankaD. Evaluation of anti-metastatic potential of the combination of fisetin with paclitaxel on A549 non-small cell lung cancer cells.Int. J. Mol. Sci.201819366110.3390/ijms19030661 29495431
    [Google Scholar]
  61. WisniewskaK.A. WisniewskaH.M. TadrowskiT. GagatM. GrzankaD. GrzankaA. Paclitaxel and the dietary flavonoid fisetin: A synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells.Cancer Cell Int.20161611010.1186/s12935‑016‑0288‑3 26884726
    [Google Scholar]
  62. TouilY.S. SeguinJ. SchermanD. ChabotG.G. Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice.Cancer Chemother. Pharmacol.201168244545510.1007/s00280‑010‑1505‑8 21069336
    [Google Scholar]
  63. MahieuxR.M. SeguinJ. VieillardV. Co-encapsulation of fisetin and cisplatin into liposomes: Stability considerations and in vivo efficacy on lung cancer animal model.Int. J. Pharm.202465112374410.1016/j.ijpharm.2023.123744 38145778
    [Google Scholar]
  64. ChenY.X. WangC.J. XiaoD.S. eIF3a R803K mutation mediates chemotherapy resistance by inducing cellular senescence in small cell lung cancer.Pharmacol. Res.202117410593410.1016/j.phrs.2021.105934 34648968
    [Google Scholar]
  65. KammerudS.C. MetgeB.J. ElhamamsyA.R. Novel role of the dietary flavonoid fisetin in suppressing rRNA biogenesis.Lab. Invest.2021101111439144810.1038/s41374‑021‑00642‑1 34267320
    [Google Scholar]
  66. ShahbazM. KamranS.H. AnwarR. Amelioration of bleomycin and methotrexate-induced pulmonary toxicity by serratiopeptidase and fisetin.Nutr. Cancer20217311-122774278410.1080/01635581.2020.1860242 33353415
    [Google Scholar]
  67. HussainT. AttasA.O.S. AlameryS. AhmedM. OdeibatH.A.M. AlrokayanS. The plant flavonoid, fisetin alleviates cigarette smoke‐induced oxidative stress, and inflammation in Wistar rat lungs.J. Food Biochem.2019438e1296210.1111/jfbc.12962 31368542
    [Google Scholar]
  68. KalimuthuS. KwonS.K. Cell survival and apoptosis signaling as therapeutic target for cancer: Marine bioactive compounds.Int. J. Mol. Sci.20131422334235410.3390/ijms14022334 23348928
    [Google Scholar]
  69. ElmoreS. Apoptosis: A review of programmed cell death.Toxicol. Pathol.200735449551610.1080/01926230701320337 17562483
    [Google Scholar]
  70. MelloS.S. AttardiL.D. Deciphering p53 signaling in tumor suppression.Curr. Opin. Cell Biol.201851657210.1016/j.ceb.2017.11.005 29195118
    [Google Scholar]
  71. EckhartL. BallaunC. HermannM. Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire.Mol. Biol. Evol.200825583184110.1093/molbev/msn012 18281271
    [Google Scholar]
  72. KoenigU. EckhartL. TschachlerE. Evidence that caspase-13 is not a human but a bovine gene.Biochem. Biophys. Res. Commun.200128551150115410.1006/bbrc.2001.5315 11478774
    [Google Scholar]
  73. SalehM. VaillancourtJ.P. GrahamR.K. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms.Nature20044296987757910.1038/nature02451 15129283
    [Google Scholar]
  74. StoweI. LeeB. KayagakiN. Caspase‐11: Arming the guards against bacterial infection.Immunol. Rev.20152651758410.1111/imr.12292 25879285
    [Google Scholar]
  75. DeneckerG. OvaereP. VandenabeeleP. DeclercqW. Caspase-14 reveals its secrets.J. Cell Biol.2008180345145810.1083/jcb.200709098 18250198
    [Google Scholar]
  76. ParraO.I. NavarroM. LuevanoC.K. Apoptosis activation in human lung cancer cell lines by a novel synthetic peptide derived from Conus californicus venom.Toxins2016823810.3390/toxins8020038 26861394
    [Google Scholar]
  77. FennellD.A. Caspase regulation in non-small cell lung cancer and its potential for therapeutic exploitation.Clin. Cancer Res.20051162097210510.1158/1078‑0432.CCR‑04‑1482 15788654
    [Google Scholar]
  78. ParkJ.Y. ParkJ.M. JangJ.S. Caspase 9 promoter polymorphisms and risk of primary lung cancer.Hum. Mol. Genet.200615121963197110.1093/hmg/ddl119 16687442
    [Google Scholar]
  79. ShivapurkarN. ReddyJ. ChaudharyP.M. GazdarA.F. Apoptosis and lung cancer: A review.J. Cell. Biochem.200388588589810.1002/jcb.10440 12616528
    [Google Scholar]
  80. PoreM.M. HiltermannT.J.N. KruytF.A.E. Targeting apoptosis pathways in lung cancer.Cancer Lett.2013332235936810.1016/j.canlet.2010.09.012 20974517
    [Google Scholar]
  81. BrambillaE. NegoescuA. GazzeriS. Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors.Am. J. Pathol.1996149619411952 8952529
    [Google Scholar]
  82. VirmaniA. RathiA. SugioK. Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer.Int. J. Cancer2003106219820410.1002/ijc.11206 12800194
    [Google Scholar]
  83. TeitzT. WeiT. ValentineM.B. Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN.Nat. Med.20006552953510.1038/75007 10802708
    [Google Scholar]
  84. SabarwalA RooyenvJC CaburetJ A novel 4′‐brominated derivative of fisetin induces cell cycle arrest and apoptosis and inhibits EGFR/ERK1/2/STAT3 pathways in non‐small‐cell lung cancer without any adverse effects in mice.FASEB J.20223612e2265410.1096/fj.202200669RR 36421014
    [Google Scholar]
  85. KangS. KimJ.H. HongJ. MoonJ.H. KwonY.Y. KoS.G. SH005S7 overcomes primary and acquired resistance of non-small cell lung cancer by combined MET/EGFR/HER3 inhibition.BioMed Res. Int.20222022111410.1155/2022/1840541 36158893
    [Google Scholar]
  86. LiX. HeS. MaB. Autophagy and autophagy-related proteins in cancer.Mol. Cancer202019111610.1186/s12943‑019‑1085‑0 31901224
    [Google Scholar]
  87. YuL. ChenY. ToozeS.A. Autophagy pathway: Cellular and molecular mechanisms.Autophagy201814220721510.1080/15548627.2017.1378838 28933638
    [Google Scholar]
  88. HansenT.E. JohansenT. Following autophagy step by step.BMC Biol.2011913910.1186/1741‑7007‑9‑39 21635796
    [Google Scholar]
  89. MizushimaN. Autophagy: Process and function.Genes Dev.200721222861287310.1101/gad.1599207 18006683
    [Google Scholar]
  90. KlionskyD.J. CreggJ.M. DunnW.A.Jr A unified nomenclature for yeast autophagy-related genes.Dev. Cell20035453954510.1016/S1534‑5807(03)00296‑X 14536056
    [Google Scholar]
  91. LiuG. PeiF. YangF. Role of autophagy and apoptosis in non-small-cell lung cancer.Int. J. Mol. Sci.201718236710.3390/ijms18020367 28208579
    [Google Scholar]
  92. YunC.W. LeeS.H. The roles of autophagy in cancer.Int. J. Mol. Sci.20181911346610.3390/ijms19113466 30400561
    [Google Scholar]
  93. LiuY. WuL. AoH. Prognostic implications of autophagy-associated gene signatures in non-small cell lung cancer.Aging20191123114401146210.18632/aging.102544 31811814
    [Google Scholar]
  94. XieK. LiangC. LiQ. Role of ATG 10 expression quantitative trait loci in non‐small cell lung cancer survival.Int. J. Cancer201613971564157310.1002/ijc.30205 27225307
    [Google Scholar]
  95. ChenJ. ZhangL. ZhouH. Inhibition of autophagy promotes cisplatin-induced apoptotic cell death through Atg5 and Beclin 1 in A549 human lung cancer cells.Mol. Med. Rep.20181756859686510.3892/mmr.2018.8686 29512762
    [Google Scholar]
  96. BhatT.A. NambiarD. PalA. AgarwalR. SinghR.P. Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention.Carcinogenesis201233238539310.1093/carcin/bgr282 22139440
    [Google Scholar]
  97. LeeH.S. JungJ.I. KimK.H. ParkS.J. KimE.J. Toxicodendron vernicifluum Stokes extract inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.PLoS One20201511e024180510.1371/journal.pone.0241805 33152052
    [Google Scholar]
  98. BrabletzT. KalluriR. NietoM.A. WeinbergR.A. EMT in cancer.Nat. Rev. Cancer201818212813410.1038/nrc.2017.118 29326430
    [Google Scholar]
  99. SaitohM. Involvement of partial EMT in cancer progression.J. Biochem.2018164425726410.1093/jb/mvy047 29726955
    [Google Scholar]
  100. XiaoD. HeJ. Epithelial mesenchymal transition and lung cancer.J. Thorac. Dis.201023154159 22263037
    [Google Scholar]
  101. TanabeS. MechanismE.M.T. EMT mechanism, lung cancer metastasis, and microRNA.Front. Mol. Biosci.2021873178810.3389/fmolb.2021.731788 34660694
    [Google Scholar]
  102. SoltermannA. Epithelial−mesenchymal transition in non-small cell lung cancer.Pathologe201233S2Suppl. 231131710.1007/s00292‑012‑1635‑3 23080026
    [Google Scholar]
  103. JakobsenK.R. DemuthC. SorensenB.S. NielsenA.L. The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.Transl. Lung Cancer Res.20165217218210.21037/tlcr.2016.04.07 27186512
    [Google Scholar]
  104. TsoukalasN. FatorouA.E. ToliaM. Epithelial–mesenchymal transition in non small-cell lung cancer.Anticancer Res.20173741773177810.21873/anticanres.11510 28373440
    [Google Scholar]
  105. CreightonC.J. LiX. LandisM. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features.Proc. Natl. Acad. Sci. USA200910633138201382510.1073/pnas.0905718106 19666588
    [Google Scholar]
  106. LuoJ. ManningB.D. CantleyL.C. Targeting the PI3K-Akt pathway in human cancer.Cancer Cell20034425726210.1016/S1535‑6108(03)00248‑4 14585353
    [Google Scholar]
  107. OsakiM. OshimuraM. ItoH. PI3K-Akt pathway: Its functions and alterations in human cancer.Apoptosis20049666767610.1023/B:APPT.0000045801.15585.dd 15505410
    [Google Scholar]
  108. MayerI.A. ArteagaC.L. The PI3K/AKT pathway as a target for cancer treatment.Annu. Rev. Med.2016671112810.1146/annurev‑med‑062913‑051343 26473415
    [Google Scholar]
  109. SarrisE. SaifM. SyrigosK. The biological role of PI3K pathway in lung cancer.Pharmaceuticals20125111236126410.3390/ph5111236 24281308
    [Google Scholar]
  110. SchefflerM. BosM. GardiziM. PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies.Oncotarget2015621315132610.18632/oncotarget.2834 25473901
    [Google Scholar]
  111. YamamotoH. ShigematsuH. NomuraM. PIK3CA mutations and copy number gains in human lung cancers.Cancer Res.200868176913692110.1158/0008‑5472.CAN‑07‑5084 18757405
    [Google Scholar]
  112. BalsaraB.R. PeiJ. MitsuuchiY. Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions.Carcinogenesis200425112053205910.1093/carcin/bgh226 15240509
    [Google Scholar]
  113. MassionP.P. TaflanP.M. ShyrY. Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression.Am. J. Respir. Crit. Care Med.2004170101088109410.1164/rccm.200404‑487OC 15317667
    [Google Scholar]
  114. ScrimaM. MarcoD.C. FabianiF. Signaling networks associated with AKT activation in non-small cell lung cancer (NSCLC): New insights on the role of phosphatydil-inositol-3 kinase.PLoS One201272e3042710.1371/journal.pone.0030427 22363436
    [Google Scholar]
  115. JiangJ. XuY. RenH. MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively regulating the PI3K/Akt pathway.J. Exp. Clin. Cancer Res.201837118910.1186/s13046‑018‑0855‑7 30103781
    [Google Scholar]
  116. RamírezP.C. GarreC.M. MolinaM.Á. DáderF.M.J. HernándezC.M.Á. PTEN and PI3K/AKT in non-small-cell lung cancer.Pharmacogenomics201516161843186210.2217/pgs.15.122 26555006
    [Google Scholar]
  117. LaplanteM. SabatiniD.M. mTOR signaling at a glance.J. Cell Sci.2009122203589359410.1242/jcs.051011 19812304
    [Google Scholar]
  118. SaxtonR.A. SabatiniD.M. mTOR signaling in growth, metabolism, and disease.Cell2017168696097610.1016/j.cell.2017.02.004 28283069
    [Google Scholar]
  119. LaplanteM. SabatiniD.M. mTOR signaling in growth control and disease.Cell2012149227429310.1016/j.cell.2012.03.017 22500797
    [Google Scholar]
  120. ZouZ. TaoT. LiH. ZhuX. mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges.Cell Biosci.20201013110.1186/s13578‑020‑00396‑1 32175074
    [Google Scholar]
  121. DingL. GetzG. WheelerD.A. Somatic mutations affect key pathways in lung adenocarcinoma.Nature200845572161069107510.1038/nature07423 18948947
    [Google Scholar]
  122. DobashiY. SuzukiS. MatsubaraH. KimuraM. EndoS. OoiA. Critical and diverse involvement of Akt/mammalian target of rapamycin signaling in human lung carcinomas.Cancer2009115110711810.1002/cncr.23996 19090006
    [Google Scholar]
  123. DobashiY. SuzukiS. KimuraM. Paradigm of kinase-driven pathway downstream of epidermal growth factor receptor/Akt in human lung carcinomas.Hum. Pathol.201142221422610.1016/j.humpath.2010.05.025 21040950
    [Google Scholar]
  124. DobashiY. WatanabeY. MiwaC. SuzukiS. KoyamaS. Mammalian target of rapamycin: A central node of complex signaling cascades.Int. J. Clin. Exp. Pathol.201145476495 21738819
    [Google Scholar]
  125. HuaH. KongQ. ZhangH. WangJ. LuoT. JiangY. Targeting mTOR for cancer therapy.J. Hematol. Oncol.20191217110.1186/s13045‑019‑0754‑1 31277692
    [Google Scholar]
  126. WufuerY. YangX. GuoL. The antitumor effect and mechanism of total flavonoids from Coreopsis tinctoria nutt (snow Chrysanthemum) on lung cancer using network pharmacology and molecular docking.Front. Pharmacol.20221376178510.3389/fphar.2022.761785 35350758
    [Google Scholar]
  127. ZhangW. LiuH.T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells.Cell Res.200212191810.1038/sj.cr.7290105 11942415
    [Google Scholar]
  128. FangJ.Y. RichardsonB.C. The MAPK signalling pathways and colorectal cancer.Lancet Oncol.20056532232710.1016/S1470‑2045(05)70168‑6 15863380
    [Google Scholar]
  129. GuoY.J. PanW.W. LiuS.B. ShenZ.F. XuY. HuL.L. ERK/MAPK signalling pathway and tumorigenesis.Exp. Ther. Med.202019319972007 32104259
    [Google Scholar]
  130. PanX. PeiJ. WangA. Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy.Acta Pharm. Sin. B20221252171219210.1016/j.apsb.2021.12.022 35646548
    [Google Scholar]
  131. KidgerA.M. SipthorpJ. CookS.J. ERK1/2 inhibitors: New weapons to inhibit the RAS-regulated RAF-MEK1/2-ERK1/2 pathway.Pharmacol. Ther.2018187456010.1016/j.pharmthera.2018.02.007 29454854
    [Google Scholar]
  132. SullivanR.J. InfanteJ.R. JankuF. First-in-class ERK1/2 inhibitor ulixertinib (BVD-523) in patients with MAPK mutant advanced solid tumors: Results of a phase I dose-escalation and expansion study.Cancer Discov.20188218419510.1158/2159‑8290.CD‑17‑1119 29247021
    [Google Scholar]
  133. TatakeR.J. O’NeillM.M. KennedyC.A. Identification of pharmacological inhibitors of the MEK5/ERK5 pathway.Biochem. Biophys. Res. Commun.2008377112012510.1016/j.bbrc.2008.09.087 18834865
    [Google Scholar]
  134. LiC. FanS. OwonikokoT.K. KhuriF.R. SunS-Y. LiR. Oncogenic role of EAPII in lung cancer development and its activation of the MAPK–ERK pathway.Oncogene201130353802381210.1038/onc.2011.94 21478903
    [Google Scholar]
  135. LinM. BiH. YanY. Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B-Raf/MAPK/Erk pathway.Oncotarget2017814234362344710.18632/oncotarget.15584 28423582
    [Google Scholar]
  136. BhattM PatelM AdnanM ReddyMN Anti-metastatic effects of lupeol via the inhibition of MAPK/ERK pathway in lung cancer, anti-cancer agents in medicinal chemistry FormCur Med Chem Anti-Cancer Agents20212122016
    [Google Scholar]
  137. PradhanR. SinghviG. DubeyS.K. GuptaG. DuaK. MAPK pathway: A potential target for the treatment of non-small-cell lung carcinoma.Future Med. Chem.2019118793795
    [Google Scholar]
  138. SeguinJ. BrulléL. BoyerR. k of the natural flavonoid fisetin improves bioavailability and antitumor efficacy.Int. J. Pharm.20134441-214615410.1016/j.ijpharm.2013.01.050 23380621
    [Google Scholar]
  139. KedarT. JalalpureS. KurangiB. Cubosomal nanoformulation increase in vitro dissolution and anticancer activity of Fisetin in A549 lung cancer cells.Ther. Deliv.2024155355369
    [Google Scholar]
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  • Article Type:
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Keyword(s): Anti-cancer drugs; anti-inflammatory; fisetin; flavonoids; lung cancer; malignancies
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