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2000
Volume 25, Issue 13
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992
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Abstract

Background

Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear.

Objective

This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma.

Methods

Here, a variety of and experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS.

Results

The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOS-induced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy.

Conclusion

These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy inhibition of the PI3K/Akt/mTOR pathway.

© 2025 The Author(s). Published by Bentham Science Publisher.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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References

  1. ArnoldM. SinghD. LaversanneM. VignatJ. VaccarellaS. MeheusF. CustA.E. VriesD.E. WhitemanD.C. BrayF. Global burden of cutaneous melanoma in 2020 and projections to 2040.JAMA Dermatol.2022158549550310.1001/jamadermatol.2022.016035353115
     [Google Scholar]
  2. SiegelR.L. MillerK.D. WagleN.S. JemalA. Cancer statistics, 2023.CA Cancer J. Clin.2023731174810.3322/caac.2176336633525
     [Google Scholar]
  3. HartmanR.I. LinJ.Y. Cutaneous melanoma—A review in detection, staging, and management.Hematol. Oncol. Clin. North Am.2019331253810.1016/j.hoc.2018.09.00530497675
     [Google Scholar]
  4. FlahertyK.T. A twenty year perspective on melanoma therapy.Pigment Cell Melanoma Res.202336656357510.1111/pcmr.1312537770281
     [Google Scholar]
  5. KimH.J. KimY.H. Molecular frontiers in melanoma: Pathogenesis, diagnosis, and therapeutic advances.Int. J. Mol. Sci.2024255298410.3390/ijms2505298438474231
     [Google Scholar]
  6. LiuS. YaoS. YangH. LiuS. WangY. Autophagy: Regulator of cell death.Cell Death Dis.2023141064810.1038/s41419‑023‑06154‑837794028
     [Google Scholar]
  7. LiX. HeS. MaB. Autophagy and autophagy-related proteins in cancer.Mol. Cancer20201911210.1186/s12943‑020‑1138‑431969156
     [Google Scholar]
  8. DebnathJ. GammohN. RyanK.M. Autophagy and autophagy-related pathways in cancer.Nat. Rev. Mol. Cell Biol.202324856057510.1038/s41580‑023‑00585‑z36864290
     [Google Scholar]
  9. JalalS. ZhangT. DengJ. WangJ. XuT. ZhangT. ZhaiC. YuanR. TengH. HuangL. β-Elemene isopropanolamine derivative LXX-8250 induces apoptosis through impairing autophagic flux via PFKFB4 repression in melanoma cells.Front. Pharmacol.20221390097310.3389/fphar.2022.90097336034839
     [Google Scholar]
  10. KashyapD. GargV.K. GoelN. Intrinsic and extrinsic pathways of apoptosis: Role in cancer development and prognosis.Adv. Protein Chem. Struct. Biol.20211257312010.1016/bs.apcsb.2021.01.00333931145
     [Google Scholar]
  11. AlvesC.L. DitzelH.J. Drugging the PI3K/AKT/mTOR pathway in ER+ breast cancer.Int. J. Mol. Sci.2023245452210.3390/ijms2405452236901954
     [Google Scholar]
  12. XuZ. HanX. OuD. LiuT. LiZ. JiangG. LiuJ. ZhangJ. Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy.Appl. Microbiol. Biotechnol.2020104257558710.1007/s00253‑019‑10257‑831832711
     [Google Scholar]
  13. TufailM. WanW.D. JiangC. LiN. Targeting PI3K/AKT/mTOR signaling to overcome drug resistance in cancer.Chem. Biol. Interact.202439611105510.1016/j.cbi.2024.11105538763348
     [Google Scholar]
  14. KharoufN. FlanaganT.W. AlamodiA.A. HmadaY.A. HassanS.Y. ShalabyH. HassanM. CD133-dependent activation of phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling in melanoma progression and drug resistance.Cells2024133240
     [Google Scholar]
  15. RahmatiM. EbrahimS. HashemiS. MotamediM. MoosaviM.A. New insights on the role of autophagy in the pathogenesis and treatment of melanoma.Mol. Biol. Rep.202047119021903210.1007/s11033‑020‑05886‑633034883
     [Google Scholar]
  16. ChamcheuJ. RoyT. UddinM. MbeumiB.S. ChamcheuR.C. WalkerA. LiuY.Y. HuangS. Role and therapeutic targeting of the PI3K/Akt/mTOR signaling pathway in skin cancer: A review of current status and future trends on natural and synthetic agents therapy.Cells20198880310.3390/cells808080331370278
     [Google Scholar]
  17. RahmanM.M. SarkerM.T. TumpaA.M.A. YaminM. IslamT. ParkM.N. IslamM.R. RaufA. SharmaR. CavaluS. KimB. Exploring the recent trends in perturbing the cellular signaling pathways in cancer by natural products.Front. Pharmacol.20221395010910.3389/fphar.2022.95010936160435
     [Google Scholar]
  18. HuangM. LuJ.J. DingJ. Natural products in cancer therapy: Past, present and future.Nat. Prod. Bioprospect.202111151310.1007/s13659‑020‑00293‑733389713
     [Google Scholar]
  19. YangY. HeP.Y. ZhangY. LiN. Natural products targeting the mitochondria in cancers.Molecules20202619210.3390/molecules2601009233379233
     [Google Scholar]
  20. DeheleanC.A. MarcoviciI. SoicaC. MiocM. CoricovacD. IurciucS. CretuO.M. PinzaruI. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy.Molecules2021264110910.3390/molecules2604110933669817
     [Google Scholar]
  21. WangQ. KuangH. SuY. SunY. FengJ. GuoR. ChanK. Naturally derived anti-inflammatory compounds from Chinese medicinal plants.J. Ethnopharmacol.2013146193910.1016/j.jep.2012.12.01323274744
     [Google Scholar]
  22. YangD. PengM. FuF. ZhaoW. ZhangB. Diosmetin ameliorates psoriasis-associated inflammation and keratinocyte hyperproliferation by modulation of PGC-1α / YAP signaling pathway.Int. Immunopharmacol.202413411224810.1016/j.intimp.2024.11224838749332
     [Google Scholar]
  23. ChenY. DaiX. ChenW. QiaoY. BaiR. DuanX. ZhangK. ChenX. LiX. MoS. CaoW. LiX. LiuK. DongZ. LuJ. Diosmetin suppresses the progression of ESCC by CDK2/Rb/E2F2/RRM2 pathway and synergies with cisplatin.Oncogene202342292278229310.1038/s41388‑023‑02750‑237349644
     [Google Scholar]
  24. LiuJ. WenX. LiuB. ZhangQ. ZhangJ. MiaoH. ZhuR. Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP-2 and MMP-9.Mol. Med. Rep.20161332401240810.3892/mmr.2016.487226847170
     [Google Scholar]
  25. SunZ. LiuK. LiangC. WenL. WuJ. LiuX. LiX. Diosmetin as a promising natural therapeutic agent: In vivo, in vitro mechanisms, and clinical studies.Phytother. Res.20243873660369410.1002/ptr.821438748620
     [Google Scholar]
  26. ZhaoF. HongX. LiD. WeiZ. CiX. ZhangS. Diosmetin induces apoptosis in ovarian cancer cells by activating reactive oxygen species and inhibiting the Nrf2 pathway.Med. Oncol.20213855410.1007/s12032‑021‑01501‑133811596
     [Google Scholar]
  27. KooshaS. MohamedZ. SinniahA. AlshawshM.A. Investigation into the molecular mechanisms underlying the anti-proliferative and anti-tumorigenesis activities of diosmetin against HCT-116 human colorectal cancer.Sci. Rep.201991514810.1038/s41598‑019‑41685‑130914796
     [Google Scholar]
  28. ChoiJ. LeeD.H. ParkS.Y. SeolJ.W. Diosmetin inhibits tumor development and block tumor angiogenesis in skin cancer.Biomed. Pharmacother.201911710909110.1016/j.biopha.2019.10909131228803
     [Google Scholar]
  29. AranhaE.S.P. PortilhoA.J.S. de SousaB.L. SilvaD.E.L. MesquitaF.P. RochaW.C. da SilvaA.F.M. LimaE.S. AlvesA.P.N.N. KoolenH.H.F. MontenegroR.C. VasconcellosM.C. 22β-hydroxytingenone induces apoptosis and suppresses invasiveness of melanoma cells by inhibiting MMP-9 activity and MAPK signaling.J. Ethnopharmacol.202126711360510.1016/j.jep.2020.11360533232779
     [Google Scholar]
  30. LiuL. WenT. XiaoY. ChenH. YangS. ShenX. Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways.J. Ethnopharmacol.202533611872610.1016/j.jep.2024.11872639181279
     [Google Scholar]
  31. JiangS. MaF. LouJ. LiJ. ShangX. LiY. WuJ. XuS. Naringenin reduces oxidative stress and necroptosis, apoptosis, and pyroptosis in random-pattern skin flaps by enhancing autophagy.Eur. J. Pharmacol.202497017645510.1016/j.ejphar.2024.17645538423240
     [Google Scholar]
  32. JeonS.J. ChoiE.Y. HanE.J. LeeS.W. MoonJ.M. JungS.H. JungJ.Y. Piperlongumine induces apoptosis via the MAPK pathway and ERK‑mediated autophagy in human melanoma cells.Int. J. Mol. Med.202352611510.3892/ijmm.2023.531837830157
     [Google Scholar]
  33. KomelT. Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanoma.Bioelectrochemistry2021141107843
     [Google Scholar]
  34. KooshaS. MohamedZ. SinniahA. AlshawshM.A. Evaluation of anti-tumorigenic effects of diosmetin against human colon cancer xenografts in athymic nude mice.Molecules20192414252210.3390/molecules2414252231295840
     [Google Scholar]
  35. ZhaoL. JinL. YangB. Diosmetin alleviates S. aureus-induced mastitis by inhibiting SIRT1/GPX4 mediated ferroptosis.Life Sci.202333112206010.1016/j.lfs.2023.12206037652155
     [Google Scholar]
  36. HeX. SunY. FanR. SunJ. ZouD. YuanY. Knockdown of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition.Mol. Ther. Oncolytics20212036437210.1016/j.omto.2021.01.01333614917
     [Google Scholar]
  37. TianL. MengH. DongX. LiX. ShiZ. LiH. ZhangL. YangY. LiuR. PeiC. LiB. IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application.Mol. Ther. Oncolytics20212018719810.1016/j.omto.2020.12.00533665357
     [Google Scholar]
  38. HazafaA. RehmanK.U. JahanN. JabeenZ. The role of polyphenol (Flavonoids) compounds in the treatment of cancer cells.Nutr. Cancer202072338639710.1080/01635581.2019.163700631287738
     [Google Scholar]
  39. NingN. LiuS. LiuX. TianZ. JiangY. YuN. TanB. FengH. FengX. ZouL. Curcumol inhibits the proliferation and metastasis of melanoma via the miR-152-3p/PI3K/AKT and ERK/NF-κB signaling pathways.J. Cancer20201171679169210.7150/jca.3862432194780
     [Google Scholar]
  40. RadS.J. OzleyenA. TumerB.T. AdetunjiO.C. OmariE.N. BalahbibA. TaheriY. BouyahyaA. MartorellM. MartinsN. ChoW.C. Natural products and synthetic analogs as a source of antitumor drugs.Biomolecules201991167910.3390/biom911067931683894
     [Google Scholar]
  41. TripoliE. GuardiaM.L. GiammancoS. MajoD.D. GiammancoM. Citrus flavonoids: Molecular structure, biological activity and nutritional properties: A review.Food Chem.2007104246647910.1016/j.foodchem.2006.11.054
     [Google Scholar]
  42. WujecM. FeldoM. Can we improve diosmetin activity? The state-of-the-art and promising research directions.Molecules202328237910
     [Google Scholar]
  43. SiQ. ShiY. HuangD. ZhangN. Diosmetin alleviates hypoxia‑induced myocardial apoptosis by inducing autophagy through AMPK activation.Mol. Med. Rep.20202221335134110.3892/mmr.2020.1124132627001
     [Google Scholar]
  44. PanZ. TanZ. LiH. WangY. DuH. SunJ. LiC. YeS. LiX. QuanJ. Diosmetin induces apoptosis and protective autophagy in human gastric cancer HGC-27 cells via the PI3K/Akt/FoxO1 and MAPK/JNK pathways.Med. Oncol.2023401131910.1007/s12032‑023‑02180‑w37796396
     [Google Scholar]
  45. RazaW. MeenaA. LuqmanS. Diosmetin: A dietary flavone as modulator of signaling pathways in cancer progression.Mol. Carcinog.20246391627164210.1002/mc.2377438888206
     [Google Scholar]
  46. NewtonK. StrasserA. KayagakiN. DixitV.M. Cell death.Cell2024187223525610.1016/j.cell.2023.11.04438242081
     [Google Scholar]
  47. KaloniD. DiepstratenS.T. StrasserA. KellyG.L. BCL-2 protein family: Attractive targets for cancer therapy.Apoptosis2023281-2203810.1007/s10495‑022‑01780‑736342579
     [Google Scholar]
  48. CzabotarP.E. SaezG.A.J. Mechanisms of BCL-2 family proteins in mitochondrial apoptosis.Nat. Rev. Mol. Cell Biol.2023241073274810.1038/s41580‑023‑00629‑437438560
     [Google Scholar]
  49. WangC. LiS. RenH. ShengY. WangT. LiM. ZhouQ. HeH. LiuC. Anti-proliferation and pro-apoptotic effects of diosmetin via modulating cell cycle arrest and mitochondria-mediated intrinsic apoptotic pathway in MDA-MB-231 cells.Med. Sci. Monit.2019254639464710.12659/MSM.91405831228347
     [Google Scholar]
  50. YanY. LiuX. GaoJ. WuY. LiY. Inhibition of TGF-β signaling in gliomas by the flavonoid diosmetin isolated from Dracocephalum peregrinum L.Molecules202025119210.3390/molecules2501019231906574
     [Google Scholar]
  51. OakC. KhalifaA. IsaliI. BhaskaranN. WalkerE. ShuklaS. Diosmetin suppresses human prostate cancer cell proliferation through the induction of apoptosis and cell cycle arrest.Int. J. Oncol.201853283584310.3892/ijo.2018.440729767250
     [Google Scholar]
  52. MizushimaN. LevineB. Autophagy in human diseases.N. Engl. J. Med.2020383161564157610.1056/NEJMra202277433053285
     [Google Scholar]
  53. FanS. YueL. WanW. ZhangY. ZhangB. OtomoC. LiQ. LinT. HuJ. XuP. ZhuM. TaoH. ChenZ. LiL. DingH. YaoZ. LuJ. WenY. ZhangN. TanM. ChenK. XieY. OtomoT. ZhouB. JiangH. DangY. LuoC. Inhibition of autophagy by a small molecule through covalent modification of the LC3 protein.Angew. Chem. Int. Ed.20216050261052611410.1002/anie.20210946434590387
     [Google Scholar]
  54. HwangH.J. HaH. LeeB.S. KimB.H. SongH.K. KimY.K. LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy.Nat. Commun.2022131143610.1038/s41467‑022‑29139‑135302060
     [Google Scholar]
  55. HuangX. YaoJ. LiuL. ChenJ. MeiL. HuangfuJ. LuoD. WangX. LinC. ChenX. YangY. OuyangS. WeiF. WangZ. ZhangS. XiangT. NeculaiD. SunQ. KongE. TateE.W. YangA. S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy.Mol. Cell2023831934853501.e1110.1016/j.molcel.2023.09.00437802024
     [Google Scholar]
  56. FengX. SunD. LiY. ZhangJ. LiuS. ZhangD. ZhengJ. XiQ. LiangH. ZhaoW. LiY. XuM. HeJ. LiuT. HasimA. MaM. XuP. MiN. Local membrane source gathering by p62 body drives autophagosome formation.Nat. Commun.2023141733810.1038/s41467‑023‑42829‑837957156
     [Google Scholar]
  57. KlionskyD.J. PetroniG. AmaravadiR.K. BaehreckeE.H. BallabioA. BoyaP. PedroB.S.J.M. CadwellK. CecconiF. ChoiA.M.K. ChoiM.E. ChuC.T. CodognoP. ColomboM.I. CuervoA.M. DereticV. DikicI. ElazarZ. EskelinenE.L. FimiaG.M. GewirtzD.A. GreenD.R. HansenM. JäätteläM. JohansenT. JuhászG. KarantzaV. KraftC. KroemerG. KtistakisN.T. KumarS. OtinL.C. MacleodK.F. MadeoF. MartinezJ. MeléndezA. MizushimaN. MünzC. PenningerJ.M. PereraR.M. PiacentiniM. ReggioriF. RubinszteinD.C. RyanK.M. SadoshimaJ. SantambrogioL. ScorranoL. SimonH.U. SimonA.K. SimonsenA. StolzA. TavernarakisN. ToozeS.A. YoshimoriT. YuanJ. YueZ. ZhongQ. GalluzziL. PietrocolaF. Autophagy in major human diseases.EMBO J.20214019e10886310.15252/embj.202110886334459017
     [Google Scholar]
  58. PangilinanC. KlionskyD.J. LiangC. Emerging dimensions of autophagy in melanoma.Autophagy20242081700171110.1080/15548627.2024.233026138497492
     [Google Scholar]
  59. SoriceM. Crosstalk of autophagy and apoptosis.Cells2022119147910.3390/cells1109147935563785
     [Google Scholar]
  60. ZhangC. LiuR. ChenM. XuY. JinX. ShenB. WangJ. Autophagy inhibitors 3‐MA and BAF may attenuate hippocampal neuronal necroptosis after global cerebral ischemia–reperfusion injury in male rats by inhibiting the interaction of the RIP3 / AIF / CypA complex.J. Neurosci. Res.20241022e2530110.1002/jnr.2530138361405
     [Google Scholar]
  61. YanJ. ShanC. ZhangZ. LiF. SunY. WangQ. HeB. LuoK. ChangJ. LiangY. Autophagy-induced intracellular signaling fractional nano-drug system for synergistic anti-tumor therapy.J. Colloid Interface Sci.202364598699610.1016/j.jcis.2023.05.03137179196
     [Google Scholar]
  62. GąsiorkiewiczB.M. AdamczykK.P. PiskaK. PękalaE. Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer.Invest. New Drugs202139253856310.1007/s10637‑020‑01032‑y33159673
     [Google Scholar]
  63. YunC.W. JeonJ. GoG. LeeJ.H. LeeS.H. The dual role of autophagy in cancer development and a therapeutic strategy for cancer by targeting autophagy.Int. J. Mol. Sci.202022117910.3390/ijms2201017933375363
     [Google Scholar]
  64. ZhangY. LiH. LvL. LuK. LiH. ZhangW. CuiT. Autophagy: Dual roles and perspective for clinical treatment of colorectal cancer.Biochimie2023206496010.1016/j.biochi.2022.10.00436244578
     [Google Scholar]
  65. HeP. HeY. MaJ. LiuY. LiuC. BaopingY. DongW. Thymoquinone induces apoptosis and protective autophagy in gastric cancer cells by inhibiting the PI3K /Akt/ mTOR pathway.Phytother. Res.20233783467348010.1002/ptr.782037288949
     [Google Scholar]
  66. DasS. ShuklaN. SinghS.S. KushwahaS. ShrivastavaR. Mechanism of interaction between autophagy and apoptosis in cancer.Apoptosis2021269-1051253310.1007/s10495‑021‑01687‑934510317
     [Google Scholar]
  67. CiechomskaI.A. The role of autophagy in cancer – characterization of crosstalk between apoptosis and autophagy; autophagy as a new therapeutic strategy in glioblastoma.Postepy Biochem.201864211912810.18388/pb.2018_12130656894
     [Google Scholar]
  68. AliMd Autophagy as a targeted therapeutic approach for skin cancer: Evaluating natural and synthetic molecular interventions.Canc. Pathog. Ther.2024204231245
     [Google Scholar]
  69. WangH. ZhaoS. LiuH. LiuY. ZhangZ. ZhouZ. WangP. QiS. XieJ. ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m 6 A-dependent manner.Int. J. Biol. Sci.20242051729174310.7150/ijbs.9299438481816
     [Google Scholar]
  70. ParkmanG.L. FothM. KircherD.A. HolmenS.L. McMahonM. The role of PI3′‐lipid signalling in melanoma initiation, progression and maintenance.Exp. Dermatol.2022311435610.1111/exd.1448934717019
     [Google Scholar]
  71. KmaL. BaruahT.J. The interplay of ROS and the PI3K/Akt pathway in autophagy regulation.Biotechnol. Appl. Biochem.202269124826410.1002/bab.210433442914
     [Google Scholar]
  72. YuL. WeiJ. LiuP. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer.Semin Canc. Biol.2022856994
     [Google Scholar]
  73. PakradooniR. ShuklaN. GuptaK. KumarJ. IsaliI. KhalifaA.O. ShuklaS. Diosmetin induces modulation of Igf-1 and Il-6 levels to alter Rictor-Akt-PKCα cascade in inhibition of prostate cancer.J. Clin. Med.20211020474110.3390/jcm1020474134682865
     [Google Scholar]
  74. PopovaN.V. JückerM. The role of mTOR signaling as a therapeutic target in cancer.Int. J. Mol. Sci.2021224174310.3390/ijms2204174333572326
     [Google Scholar]
  75. YuX. ZhangD. HuC. YuZ. LiY. FangC. QiuY. MeiZ. XuL. Combination of diosmetin with chrysin against hepatocellular carcinoma through inhibiting PI3K / AKT / mTOR / NF ‐ кB signaling pathway: TCGA analysis, molecular docking, molecular dynamics, in vitro experiment.Chem. Biol. Drug Des.20241044e7000310.1111/cbdd.7000339448547
     [Google Scholar]
  76. FarhanM. SilvaM. XinganX. ZhouZ. ZhengW. Artemisinin inhibits the migration and invasion in uveal melanoma via inhibition of the PI3K/AKT/mTOR signaling pathway.Oxid. Med. Cell. Longev.202120211991153710.1155/2021/991153734931134
     [Google Scholar]
  77. HellT. DobrzyńskiM. GröflinF. ReinhardtJ.K. DürrL. PertzO. HamburgerM. GaroE. Flavonoids from Ericameria nauseosa inhibiting PI3K/AKT pathway in human melanoma cells.Biomed. Pharmacother.202215611375410.1016/j.biopha.2022.11375436265310
     [Google Scholar]
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Effects of Citrus-derived Diosmetin on Melanoma: Induction of Apoptosis and Autophagy Mediated by PI3K/Akt/mTOR Pathway Inhibition
Anti-Cancer Agents in Medicinal Chemistry 25, 921 (2025); https://doi.org/10.2174/0118715206360266250115065234
/content/journals/acamc/10.2174/0118715206360266250115065234
/content/journals/acamc/10.2174/0118715206360266250115065234
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  • Article Type:     Research Article
Keyword(s): anti-tumor; apoptosis; autophagy; cutaneous melanoma; Diosmetin; PI3K/Akt/mTOR

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